To test the quality of the new algorithm, several well-known genes with clusters of mutually exclusive exons with different characteristics were analysed (Figure 3). The first test case is the cytoplasmic dynein heavy chain from Schistosoma mansoni (Sm DHC1). Dynein heavy chains belong to the longest genes in eukaryotes encoding 4000 - 5000 residues and are spread over several dozens of exons. The mutually exclusive exon is clearly identified in the middle of the gene, encoding split codons at the 3- and 5-end of the exon. The query exon and the candidate exon have identical lengths and show strong homology. Based on the multiple sequence alignment of more than 2000 DHCs these exons are mutually exclusive and not constitutive or differentially included. The second case represents the muscle myosin heavy chain gene from the waterflea Daphnia magna[19]. The arthropod muscle myosin heavy chain genes contain several clusters of mutually exclusive exons to fine tune the mechanochemical ...
Alternative exon usage (AEU) is an important component of gene regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival. The expression of exons corresponding to 25,403 genes was related to the survival of 250 individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training data set were confirmed in an independent validation data set of 78 patients. A hierarchical mixed model that allows the consideration of covariation between exons within a gene and of
This track shows the genomic locations of the probesets and probes from the Affymetrix Exon array. This array was designed to interrogate every known and putative exon in the human genome. For the design of this array, Affymetrix compiled evidence of expression from sources including well-annotated genes such as RefSeq, genomic alignments of mRNA and EST sequences, gene predictions, exon predictions, and regions that are syntenic to conserved regions in related species. Using this evidence, Affymetrix designed a probeset for each known or putative exon. While some of these regions might never be transcribed, the goal is to obtain a comprehensive measurement of transcription in the human genome. In most cases, this array contains one probeset per exon. However, whenever this design-time evidence suggested that some exon had alternative splice sites, the exon was subdivided into two or more regions, and one probeset was designed for each region (where possible). The array contains no probesets for ...
An additional nicety would be to somehow work in a preference for 5 exons. For example, lets say a gene has 3 exons and, with the expression data, all 3 exons are equally expressed. Id like to selectively get the first 2 exons. Ive started learning Galaxy and was able to import BED files for UCSC exons (as in the Galaxy 101 tutorial) and a BED file for Affy microarray expression data. (I tried also importing the Burge RNA-seq track as BED but couldnt get it to work). I did an inner join on genomic sequences to join the expression data with the exons and sorted them from most expressed to least. But how do I sort within genes? That is, how do I get the top 2 exons per gene (highest expressing exons per gene) and, if there are more than 2 with equally high expression, how do I preferentially get the 5` exons? Im also open to ways to do this without using Galaxy, etc. I want to do this for an entire genome, so I figured it would be good to have a Galaxy workflow, which I could then apply to ...
Exon shuffling was first introduced in 1978 when Walter Gilbert discovered that the existence of introns could play a major role in the evolution of proteins. It was noted that recombination within introns could help assort exons independently and that repetitive segments in the middle of introns could create hotspots for recombination to shuffle the exonic sequences. However, the presence of these introns in eukaryotes and absence in prokaryotes created a debate about the time in which these introns appeared. Two theories arose: the "introns early" theory and the "introns late" theory. Supporters of the "introns early theory" believed that introns and RNA splicing were the relics of the RNA world and therefore both prokaryotes and eukaryotes had introns in the beginning. However, prokaryotes eliminated their introns in order to obtain a higher efficiency, while eukaryotes retained the introns and the genetic plasticity of the ancestors. On the other hand, supporters of the "introns late" theory ...
TY - JOUR. T1 - Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene. AU - Fukumura, Kazuhiro. AU - Kato, Ayako. AU - Jin, Yui. AU - Ideue, Takashi. AU - Hirose, Tetsuro. AU - Kataoka, Naoyuki. AU - Fujiwara, Toshinobu. AU - Sakamoto, Hiroshi. AU - Inoue, Kunio. PY - 2007/8/1. Y1 - 2007/8/1. N2 - Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing repressor to induce exon skipping. Here we report the mechanism of exon skipping regulated by Fox-1, using the hF1γ gene as a model system. We found that Fox-1 induces exon 9 skipping by repressing splicing of the downstream intron 9 ...
Due to the inclusive nature of our genome-wide exon microarrays, we are able to discover novel alternative splicing patterns in addition to monitoring known splicing events. As technology allows for smaller feature sizes, it will be possible to include larger numbers of probes per array, thereby increasing the feasibility of large-scale non-biased designs. Microarray designs that are more inclusive and less dependent on current genome annotations will ultimately aid in the development of tools that are designed to annotate, rather than the other way around. For example, recent work using a similar design concept based on the mouse genome was able to refine gene boundaries using co-regulation of exons across many different tissue types [43]. However, our data suggest that there is a large amount of expression outside of well annotated exons. Reliance on any one single exon prediction algorithm or sequence content source will likely result in incomplete coverage.. Exon microarrays represent a huge ...
Genemark = Bio::Tools::Genemark-,new(-file =, result.Genemark); # filehandle: $Genemark = Bio::Tools::Genemark-,new( -fh =, \*INPUT ); # parse the results # note: this class is-a Bio::Tools::AnalysisResult which implements # Bio::SeqAnalysisParserI, i.e., $Genemark-,next_feature() is the same while($gene = $Genemark-,next_prediction()) { # $gene is an instance of Bio::Tools::Prediction::Gene, which inherits # off Bio::SeqFeature::Gene::Transcript. # # $gene-,exons() returns an array of # Bio::Tools::Prediction::Exon objects # all exons: @exon_arr = $gene-,exons(); # initial exons only @init_exons = $gene-,exons(Initial); # internal exons only @intrl_exons = $gene-,exons(Internal); # terminal exons only @term_exons = $gene-,exons(Terminal); # singleton exons: ($single_exon) = $gene-,exons(); } # essential if you gave a filename at initialization (otherwise the file # will stay open) $Genemark-,close ...
Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3.: The functional implications of the dopamine D4 receptor gene (DRD4) exon II
Comparative analysis of exon/intron organization of genes and their resulting protein structures is important for understanding evolutionary relationships between species, rules of protein organization, and protein functionality. We present SEDB, the Structural Exon Database, with a web interface, an application which allows users to retrieve the exon/intron organization of genes and map the location of the exon boundaries and intron phase onto a multiple structural alignment. SEDB is linked with Friend, an integrated analytical multiple sequence/structure viewer, which allows simultaneous visualization of exon boundaries on structure and sequence alignments. With SEDB researchers can study the correlations of gene structure with the properties of the encoded three-dimensional protein structures across eukaryotic organisms ...
The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a ,95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection. Moreover, the extensive epistasis in the landscape predicts that exonic regulatory sequences may diverge between species even when exon inclusion levels are functionally important and conserved by selection ...
The recently released Exon arrays differ from the previous 3 arrays in terms of the number, placement and annotational confidence of oligonucleotide probes. As a result, new methods that take advantage of Exon array design features can improve gene-level expression estimates. In this manuscript we propose a strategy for computing gene expression indices on Exon arrays that combines a probe-specific background correction with a probe selection procedure. Analysis of independent SAGE data demonstrates that A/P calls generated from the MAT background model offer substantial improvements. This improvement is likely due to both the increased number of probes per gene and the improvement of the MAT background model over the default Affymetrix background correction. Furthermore, we observed that Exon array gene expression indices show a high degree of correlation between human and mouse orthologs.. This work represents a step in the continued development of accurate gene-level expression estimates ...
Although unicellular eukaryotes such as yeast have either no introns or very few, metazoans and especially vertebrate genomes have a large fraction of non-coding DNA. For instance, in the human genome only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA.[5] This can provide a practical advantage in omics-aided health care (such as precision medicine) because it makes commercialized whole exome sequencing a smaller and less expensive challenge than commercialized whole genome sequencing. The large variation in genome size and C-value across life forms has posed an interesting challenge called the C-value enigma. Across all eukaryotic genes in GenBank there were (in 2002), on average, 5.48 exons per gene. The average exon encoded 30-36 amino acids.[6] While the longest exon in the human genome is 11555 bp long, several exons have been found to be only 2 bp long.[7] A single-nucleotide exon has been reported from the Arabidopsis ...
patients (13% of all patients), while exon 45 and 53 skipping would both individually be applicable to 8% of the patients (Aartsma-Rus et al. 2009a). AONs to skip each individual exon have been identified and theoretically exon skipping would be applicable to 80% of deletions, 91% of small mutations and 73% of duplications, or 83% of all patients (Table 5.2).. However, mutations in the essential cysteine-rich domain invariably cause DMD, regardless of whether deletions are in-frame or out-of-frame (Aartsma-Rus et al. 2006b). Thus, for patients with mutations in the part of the transcripts that encodes the cysteine-rich domain (exons 64-70, Fig. 5.1) exon skipping will in all likelihood not be beneficial. Since there are two N-terminal actin-binding domains, and a third domain located in the central rod domain (Fig. 5.1), there is more flexibility for deletions affecting one or two actin-binding domains, as the additional domains retain some of the functionality (Aartsma-Rus et al. 2006b). ...
Detection of exon junctions in single cells within the tissue environment is possible by using only one ZZ probe uniquely designed on the specific exon junction of interest. For an example of the detection of a sequence with specific exon skipping, METΔ14 (Frampton GM et al, Cancer Discovery, 2015; Awad MM et al, J Clin Oncol, 2016) where 3 probes are designed (image 1): one control probe designed for an exon junction present in all MET transcripts (exon junction 12/13), one probe designed for the exon junction with exon 14 (exon junction 14/15), and one probe designed for the exon junction with exon 14 skipping (exon junction 13/15). Figure 2 shows an example of the BaseScope™ assay used for the detection of METΔ14 in cell lines ...
Tumor-predominant splice isoforms were identified during comparative in silico sequence analysis of EST clones, suggesting that global aberrant alternative pre-mRNA splicing may be an epigenetic phenomenon in cancer. We used an exon expression array to perform an objective, genome-wide survey of glioma-specific splicing in 24 GBM and 12 nontumor brain samples. Validation studies were performed using RT-PCR on glioma cell lines, patient tumor and nontumor brain samples. In total, we confirmed 14 genes with glioma-specific splicing; seven were novel events identified by the exon expression array (A2BP1, BCAS1, CACNA1G, CLTA, KCNC2, SNCB, and TPD52L2). Our data indicate that large changes (| 5-fold) in alternative splicing are infrequent in gliomagenesis (| 3% of interrogated RefSeq entries). The lack of splicing changes may derive from the small number of splicing factors observed to be aberrantly expressed. While we observed some tumor-specific alternative splicing, the number of genes showing exclusive
Abstract: Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed.For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62), by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons.The correction of DMD duplications by exon skipping depends on the specific exons ...
An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature messenger RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome. The term exon derives from the expressed region and was coined by American biochemist Walter Gilbert in 1978: "The notion of the cistron… must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger - which I suggest we call introns (for intragenic regions) - alternating with regions which will be expressed - exons." This definition was originally made for protein-coding transcripts that are spliced before being translated. The term later ...
The Fgf2 gene is expressed in the brain neuroepithelium during embryonic development and in astroglial cells throughout life. Previous knockout studies suggested that FGF2 plays a role in the proliferation of neural progenitors in the embryonic cerebral cortex. These studies exclusively used knockout alleles lacking the Fgf2 exon 1. However, the description of putative alternative exons located downstream from the canonical exon 1 raised the possibility that alternatively spliced transcripts may compensate for the lack of the canonical exon 1 in the Fgf2 -/- mice. We generated and characterized a new line of Fgf2 knockout mice lacking the expression of exon 3, which is conserved in all Fgf2 transcripts and contains essential heparin and receptor binding interfaces. The expression of Fgf2 exon 3 was prevented by inserting a transcriptional STOP cassette in the Fgf2 genomic locus. These mice demonstrate a phenotype in the adult neocortex characterized by decreased density and number of cortical excitatory
mzef = Bio::Tools::MZEF-,new(-file =, result.mzef); # filehandle: $mzef = Bio::Tools::MZEF-,new( -fh =, \*INPUT ); # to indicate that the sequence was reversed prior to feeding it to MZEF # and that you want to have this reflected in the strand() attribute of # the exons, as well have the coordinates translated to the non-reversed # sequence $mzef = Bio::Tools::MZEF-,new( -file =, result.mzef, -strand =, -1 ); # parse the results # note: this class is-a Bio::Tools::AnalysisResult which implements # Bio::SeqAnalysisParserI, i.e., $genscan-,next_feature() is the same while($gene = $mzef-,next_prediction()) { # $gene is an instance of Bio::Tools::Prediction::Gene # $gene-,exons() returns an array of # Bio::Tools::Prediction::Exon objects # all exons: @exon_arr = $gene-,exons(); # internal exons only @intrl_exons = $gene-,exons(Internal); # note that presently MZEF predicts only internal exons! } # essential if you gave a filename at initialization (otherwise the file # will stay open) ...
In human pre-mRNA splicing, infrequent errors occur resulting in erroneous splice products as shown in a genome-wide approach. One characteristic subgroup consists of products lacking one cassette exon. The noise in the splicing process, represented by those misspliced products, can be increased by cold shock treatment or by inhibiting the nonsense mediated decay. Here, we investigated whether the splicing noise frequency increases with age in vivo in peripheral bloods cells or in vitro in cultured and aged fibroblasts from healthy donors. Splicing noise frequency was measured for four erroneously skipped NF1 exons and one exon of RABAC1, AATF and PCGF2 by RT-qPCR. Measurements were validated in cultured fibroblasts treated with cold shock or puromycin. Intragenic but not interpersonal differences were detected in splicing noise frequencies in vivo in peripheral blood cells of 11 healthy donors (15 y-85 y) and in in vitro senescent fibroblasts from three further donors. No correlation to the age of the
While, characterizing the hAT1R gene it was demonstrated that ≥4 alternatively spliced hAT1R mRNAs were transcribed in human tissues (Figure 1).33,34 The hAT1R mRNA splice variants were composed of the following exons: exons 1 and 4; exons 1, 2, and 4; exons 1, 3, and 4; and exons 1, 2, 3, and 4; therefore, alternatively spliced hAT1R mRNAs differ only in the inclusion or exclusion of exon 2 and/or 3 (reviewed in Reference 37).. Splice variants that harbor exon 2 are functionally interesting because they contain 2 upstream AUG start codons (Figure 1),34,38 which are predicted to generate upstream ORFs (uORFs) of different lengths. PCR analysis demonstrated that hAT1R mRNA splice variants, which included exon 2 (ie, exons 1, 2, and 4), were composed of ≥30% of the total hAT1R mRNA transcripts expressed in a given tissue; this suggests that this splice variant is physiologically important.34,38-40 Curnow et al34 and Warnecke et al38 demonstrated that the presence of exon 2 inhibited the ...
The genetic change was a single base (G) insertion in exon 25 of the cardiac MyBP-C gene on chromosome 11, which resulted in a sequence suitable to serve as a 5′ splice donor site (AG GTGGG). This mutation was also recently reported in a nonrelated family of the same ethnic group in North America.10 We showed that the mutation resulted in the loss of 40 bp at the 3′ end of exon 25 in mRNA extracted from affected myocardial tissue. This loss resulted in a premature translational stop, which was then predicted to result in a truncated protein of 95 kDa and the loss of the C-terminal binding sites for myosin heavy chain and titin.20 A reading shift would also occur if mRNA splicing were unaffected by the inserted G in exon 25. In this case, the shift resulting from the additional G would lead to a premature stop 40 residues away from the 3′ terminal of codon 792. However, such mutated mRNA was not observed (data not shown).. The shortened 95-kDa MyBP-C protein was not detected in ...
DNA is made up of different units called nucleotides. There are a variety of four different nucleotides that make up the polymer that is DNA[1]. DNA consists of two different regions, one being exons and the other introns. The regions of exons in the DNA consist of fewer nucleotides than the regions of introns and are the regions that code for proteins[2]. It is also now thought that enhancer sequences for regulation of gene transcription is not just found in introns but also exons.[3]. Exons are the coding regions of a gene and are separated by regions of introns; they are copied during transcription (along with introns) to produce pre-mRNA[4] ...
OBJECTIVE: To investigate the expression of the familial Mediterraneanfever (FMF) gene (MEFV) in human synovial fibroblasts. METHODS: MEFVmessenger RNA in synovial fibroblasts, chondrocytes, and peripheral bloodleukocytes (PBLs) was analyzed by semiquantitative and real-timepolymerase chain reaction and ribonuclease protection assay. Thesubcellular localization of pyrin, the MEFV product, was determined intransfected synovial fibroblasts and HeLa cells with plasmids encodingpyrin isoforms. Native pyrin was detected with an antipyrin antibody.RESULTS: MEFV was expressed in synovial fibroblasts, but not inchondrocytes. Four alternatively spliced transcripts were identified: anextension of exon 8 (exon 8ext) resulting in a frameshift that predicts atruncated protein lacking exons 9 and 10, the addition of an exon (exon4a) predicting a truncated protein at exon 5, the in-frame substitution ofexon 2a for exon 2, and the previously described removal of exon 2 (exon2Delta). Exon 8ext transcripts ...
The classification of human gene sequences into exons and introns is a difficult problem in DNA sequence analysis. In this paper, we define a set of features, called the simple Z (SZ) features, which is derived from the Z-curve features for the recognition of human exons and introns. The classification results show that SZ features, while fewer in numbers ~three in total!, can preserve the high recognition rate of the original nine Z-curve features. Since the size of SZ features is one-third of the Z-curve features, the dimensionality of the feature space is much smaller, and better recognition efficiency is achieved. If the stop codon feature is used together with the three SZ features, a recognition rate of up to 92% for short sequences of length ,140 bp can be obtained ...
The complete exon size and distribution pattern in the gene for the alpha 1 chain of human type IV collagen was determined. Clones covering 145 kilobases (kb) of genomic DNA including 100 kb of the gene itself as well as 25 kb upstream and 20 kb downstream of the gene sequences, respectively, were isolated from lambda phage and cosmid libraries. The overall gene structure was determined by endonuclease restriction mapping and R-loop analyses and all exon sizes by nucleotide sequencing. The characterized clones contained all the coding sequences except for exon 2 whose sequence was determined after its amplification by the polymerase chain reaction. There were four gaps in the intron sequences; the exact size of the gene is unknown. The entire gene is at least 100 kb in size and contains 52 exons whose size distribution is completely different from that of the genes for fibrillar collagens. In the -Gly-X-Y- coding region there are three exons of 99, 90, and 45 base pairs (bp) each and two exons ...
Hi everyone, I need a bed file containing starts and ends of the exons, gene name and number of the exon - but just for the canonical transcript - because I dont want to have the regions repeated. I tried UCSC Table browser and BioMart but non of them gives me exactly what I need.. Using UCSC I can get canonical transcripts (but at the same time I couldnt get starts and ends of the exon altogether with the gene name).. Using BioMart I can get starts and ends of the exons altogether with the gene name, but I cant find how to choose the canonical transcripts and thats why the regions are repeated as seen below in the case of NUS1P3:. ...
In this work, organization, expression and function of the human Peroxisomal Testis-specific 1 (PXT1) gene were investigated. The mRNA of the human PXT1 gene doesnt contain two exons as known so far, but five exons. The expression of three putative upstream exons was confirmed in this work. The results of the qualitative and quantitative real-time PCR show that the exon 1 consists of three variously spliced units (exons 1a, 1b and 1c). The human PXT1 gene is subjected to alternative splicing, of which exons 1b, 1c, 2 and 4 are concerned, which was shown by sequence analysis. In total, six transcripts were identified. The additional exons have an impact on the protein structure due to the extension of the ORF coding for 51 amino acids previously to 134 now. In the longer protein the BH3 interacting domain (BID) is detected which has a known proapoptotic function. Due to the alternatively spliced exon 4 and the resulting frameshift a truncated protein exists and in its mRNA a premature stop codon ...
Nous montrons lutilisation de la puce exon dAffymetrix pour lanalyse simultanée de lexpression des gènes et de la variation disoformes. Nous avons utilisé les échantillons dARN du cerveau et des tissus de référence qui ont été antérieurement utilisés dans létude du consortium MicroArray Quality Control (MAQC). Nous démontrons une forte concordance de la quantification de lexpression des gènes entre trois plateformes dexpression populaires à savoir la puce exon dAffymetrix, la puce Illumina et la puce U133A dAffymetrix. Plus intéressant nous montrons que la majorité des discordances entre les trois plateformes résulterait des positions différentes des sondes à travers les plateformes et que les variations disoforme exactes ne peuvent être identifiées que par la puce exon. Nous avons détecté avec succès, entre les tissus de référence et ceux du cerveau, une centaine de cas dévènements dépissage alternatif. La puce exon est requise dans lanalyse de ...
Aims to balance the goal of giving the complete picture of possible coding exons, with the need to stay grounded in terms of the verifiability of the actual function of the sequences it collects. Thus it relies on the ENSEMBLs annotation of known (known here being the actual annotation term used, hence the quotes) human exons as the anchor for the search and for the results presentation. To these, ExoLocator adds the search for ostensibly missing exons in orthologous protein pairs across species, using an extensive computational pipeline to narrow down the search region for the candidate exons and find a suitable template in the other species, as well as state-of-the-art implementations of pairwise alignment algorithms. The resulting complements of exons are organized in a way currently unique to ExoLocator: multiple sequence alignments, both on the nucleotide and on the peptide levels, clearly indicating the exon boundaries. The alignments can be inspected in the web-embedded viewer, downloaded or
Author Summary Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. While transcriptional responses to infection have been well-characterized, much less is known about the extent to which co-transcriptional mechanisms of mRNA processing are involved in the regulation of immune defenses. In this study, we sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infection. Using primary human macrophages derived from whole blood samples from 60 individuals, we sequenced mRNA both before and after infection with two live bacteria. We show that immune responses to infection are accompanied by pervasive changes in mRNA isoform usage, with systematic shifts towards increased cassette exon inclusion and shortening of Tandem 3 UTRs post-infection. These patterns are conserved in nonhuman primates, supporting their functional importance across evolutionary time. Complementary microRNA
Author Summary Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. While transcriptional responses to infection have been well-characterized, much less is known about the extent to which co-transcriptional mechanisms of mRNA processing are involved in the regulation of immune defenses. In this study, we sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infection. Using primary human macrophages derived from whole blood samples from 60 individuals, we sequenced mRNA both before and after infection with two live bacteria. We show that immune responses to infection are accompanied by pervasive changes in mRNA isoform usage, with systematic shifts towards increased cassette exon inclusion and shortening of Tandem 3 UTRs post-infection. These patterns are conserved in nonhuman primates, supporting their functional importance across evolutionary time. Complementary microRNA
Does anyone have any information on these exons. I know exon skipping is not an option because of the complexity of these exons but that is where my knowledge…
Like CB1R, the CB2R coding region is contained in a single exon and is flanked by upstream noncoding exons in human, mouse, and, debatably, rat. Human CB2R consists of three exons alternatively transcribed and spliced to yield isoforms CB2A and -B (Liu et al., 2009). CB2B, the first cloned cDNA, is transcribed from a promoter proximal to exon2 and expressed most highly in immune cells and tissues. The more recently identified CB2A contains exon1 and exon3 and is generated from a promoter 5′ proximal to exon1. In contrast to CB2B, CB2A is most highly expressed in testis and shows some expression in the brain.. Mouse CB2R similarly consists of three exons alternatively transcribed by two promoters (Onaivi et al., 2006; Liu et al., 2009). In contrast to humans, however, both CB2A and CB2B are expressed predominantly in the spleen (Liu et al., 2009). Rat CB2R gene structure seems more complex than that of human and mouse, although findings are conflicting. In Fig. 1, we present findings by Liu et ...
1. In the context of a new mammalian model organism recently sequenced and annotated, gene YFG has 3 introns and 4 exons. Databases show that there are 3 different lengths of cDNA sequences associated with Gene YFG. One of these cDNA sequences has three out of four exons plus additional nucleotide sequence at the 3 end of the cDNA. This part codes for an extra 123 amino acids. Annotated gene UB2, appears immediately downstream of YFG. UB2 has a single exon coding for 123 amino acids matching the cDNA. There is no cDNA in your database encoding for a UB2 gene with these 123 amino acids at the N-terminus ...
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. Comparison of all 10 variable exons between mouse, human, and rat.
RNA modification must be performed in order to form the various proteins needed for eukaryotes to function. RNA modification generates mature RNA. Through RNA modification, a eukaryotic cell can use fewer variations in base pairs of the genetic code (DNA and RNA) while creating proteins with diverse functions. One of the most common methods employed by eukaryotes is to use spliceosomes to cleave out introns (intervening sequences/ non coding proteins) of the pre-RNA, leaving only exons (expressed sequences/coding proteins). Cutting out the intron segments allows for the possibility of exon to rearrangement. Spicing all exons together is called mature mRNA.. Whats the advantage of spitting genes? Exons are segments that coding proteins and give proteins specific functions. This leads to the concept of exon shuffling. Exons shuffling is the rearrangement of the exons in the mRNA. These mRNA will come up with different types of proteins with different functions, binding sites, and catalytic sites. ...
Supplement Genes contain exons which are regions coding for proteins and which are interrupted by the unused sequences called introns. Exons have been found to include both sequences coding for amino acids and untranslated sequences. The introns are removed and the exons are joined together to form the final functional mRNA. ...
RefSeq Summary (NM_002116): HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-A alleles have been described. [provided by RefSeq, Jul 2008 ...
Affymetrix is dedicated to developing state-of-the-art technology for acquiring, analyzing, and managing complex genetic information for use in biomedical research. Affymetrix sells GeneChip® brand microarrays.
A somewhat accidental discovery and random meetings between proteins in a cell: These are the subjects of two new online articles. Each, it its way, involves a technological advance that will, in turn, lead to further scientific discovery. The first involves a partnership between a physics group and a cancer-research group. Among other things, such…. ...
To determine exon-intron structures and genomic organization, the human and (rhesus) macaque genomes were analyzed using BLAT. The first exon (noncoding) of macaque MGST3 was predicted from the human MGST3 sequence because the identified cynomolgus/rhesus MGST cDNAs contained only the coding sequence. Among the macaque MGST sequences analyzed, the largest was MGST2 (,37 kilobases), followed by MGST3 and MGST1, similar to human sequences (Supplemental Fig. 1). Macaque MGST1, MGST2, and MGST3 contained 4, 5, and 6 exons, respectively, similar to humans (Supplemental Fig. 1). Other than the first and last exons, whose sizes vary due to inclusion of noncoding sequences, the sizes of the MGST1, MGST2, and MGST3 exons were the same in macaques and humans, ranging from 58 base pairs (bp) to 124 bp, except for exon 2 of MGST1 (158 bp in macaques and 148 bp in humans). This discrepancy might be attributable to the use of a splice acceptor site (AG) in macaque MGST1, 10 bp upstream of that of human MGST1. ...
Historically, MECP2 variants are called based on the e2 isoform (i.e. transcript containing exons 1, 2, 3 & 4, with start codon in exon 2). MECP2 variants in RettBASE are also named according to this convention, except for those directly affecting the e1 isoform (which will include the prefix MECP2_e1). Nomenclature of mutations in exon 3 and exon 4 will differ by 12 amino acids between the two isoforms (e.g. p.R306C or p.Arg306Cys in isoform e2 is equivalent to p.R318C or p.Arg318Cys in isoform e2). cDNA nomenclature will differ by 36 nucleotides.. Two refseq transcripts are available for CDKL5. Alternate exons for CDKL5 have been described (see Hector et al., 2016,Williamson et al., 2012, Fichou et al., 2011 and Rademacher et al., 2011 for details) but are not included in either reference sequence. Also refer to Diebold et al., 2014 regarding pathogenicity of CDKL5 variants in exons 19, 20 and 21. Please check our resources pages for general information on mutation nomenclature. ...
The Far UpStream Element (FUSE)-binding protein-interacting repressor (FIR), a c-myc transcriptional suppressor, is alternatively spliced removing the transcriptional repression domain within exon 2 (FIRΔexon2) in colorectal cancers. SAP155 is a subunit of the essential splicing factor 3b (SF3b) subcomplex in the spliceosome. This study aims to study the significance of the FIR-SAP155 interaction for the coordination of c-myc transcription, pre-mRNA splicing, and c-Myc protein modification, as well as to interrogate FIRΔexon2 for other functions relating to altered FIR pre-mRNA splicing. Knockdown of SAP155 or FIR was used to investigate their reciprocal influence on each other and on c-myc transcription, pre-mRNA splicing, and protein expression. Pull down from HeLa cell nuclear extracts revealed the association of FIR, FIRΔexon2, and SF3b subunits. FIR and FIRΔexon2 were coimmunoprecipitated with SAP155. FIR and FIRΔexon2 adenovirus vector (Ad-FIR and Ad-FIRΔexon2, respectively) were ...
Transcript Variant: This variant (3) lacks three alternate exons, contains three alternate exons and uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD ...
Exon sequences are conserved, but intron sequences vary, Organization of Genetic Material Split Genes, Overlapping Genes and Pseudogenes, Genetics
Alternative splicing amplifies the information content of the genome, creating multiple mRNA isoforms from single genes. The evolutionarily conserved splicing activator Tra2β (Sfrs10) is essential for mouse embryogenesis and implicated in spermatogenesis. Here we find that Tra2β is up-regulated as the mitotic stem cell containing population of male germ cells differentiate into meiotic and post-meiotic cells. Using CLIP coupled to deep sequencing, we found that Tra2β binds a high frequency of exons and identified specific G/A rich motifs as frequent targets. Significantly, for the first time we have analysed the splicing effect of Sfrs10 depletion in vivo by generating a conditional neuronal-specific Sfrs10 knock-out mouse (Sfrs10fl/fl; Nestin-Cretg/+). This mouse has defects in brain development and allowed correlation of genuine physiologically Tra2β regulated exons. These belonged to a novel class which were longer than average size and importantly needed multiple cooperative Tra2β ...
Acute Myeloid Leukemia (AML) is a clinically heterogeneous disease. Recurrent cytogenetic abnormalities help define subgroups with different prognosis and identify patients whom might benefit from targeted therapies. However, almost half adults AML cases display a normal karyotype by conventional cytogenetics, and the clinical and molecular features of this large subgroup of patients are poorly understood. The NPM exon 12 mutation can serve as predictor in AML cases with a normal karyotype, good response to induction chemotherapy and as a marker for monitoring of minimal residual disease. NPM exon 12 mutations are AML-specific since they are not detected in normal cells or other neoplasms.
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