Cleavage Stimulation Factor
mRNA Cleavage and Polyadenylation Factors
Cleavage And Polyadenylation Specificity Factor
RNA Processing, Post-Transcriptional
Molecular Sequence Data
National Institute on Alcohol Abuse and Alcoholism (U.S.)
National Institute on Aging (U.S.)
Receptor, Cannabinoid, CB1
National Institute on Drug Abuse (U.S.)
Brain-Derived Neurotrophic Factor
Proprotein Convertase 2
Cloning and characterization of Arabidopsis homologues of the animal CstF complex that regulates 3' mRNA cleavage and polyadenylation. (1/39)The 3' cleavage and polyadenylation of mRNAs has been studied in detail in animals and yeast, but not in plants. Aimed at elucidating the regulation of mRNA 3' end formation in plants, three Arabidopsis cDNAs encoding homologues of the animal proteins CstF-64, CstF-77 and CstF-50 that form the cleavage stimulating factor of the polyadenylation machinery have been cloned. It is shown experimentally that the N-terminal domain of the Arabidopsis CstF-64 homologue binds the mRNA 3' non-coding region in an analogous manner to the animal protein. It is also shown that the Arabidopsis CstF-64 and CstF-77 homologues strongly interact with each other in a similar way to their animal counterparts. These results imply that these Arabidopsis homologues belong to the polyadenylation machinery of nuclear mRNAs. (+info)
Polyadenylation: a tail of two complexes. (2/39)Recent studies have uncovered new connections between the enzymes of mRNA 3' end processing and RNA polymerase II. These connections improve the efficiency of polyadenylation and signal to the polymerase to terminate transcription; their discovery reveals another level of gene regulation. (+info)
An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation. (3/39)SRm160 (the SR-related nuclear matrix protein of 160 kDa) functions as a splicing coactivator and 3'-end cleavage-stimulatory factor. It is also a component of the splicing-dependent exon-junction complex (EJC), which has been implicated in coupling of pre-mRNA splicing with mRNA turnover and mRNA export. We have investigated whether the association of SRm160 with the EJC is important for efficient 3'-end cleavage. The EJC components RNPS1, REF, UAP56, and Y14 interact with SRm160. However, when these factors were tethered to transcripts, only SRm160 and RNPS1 stimulated 3'-end cleavage. Whereas SRm160 stimulated cleavage to a similar extent in the presence or absence of an active intron, stimulation of 3'-end cleavage by tethered RNPS1 is dependent on an active intron. Assembly of an EJC adjacent to the cleavage and polyadenylation signal in vitro did not significantly affect cleavage efficiency. These results suggest that SRm160 stimulates cleavage independently of its association with EJC components and that the cleavage-stimulatory activity of RNPS1 may be an indirect consequence of its ability to stimulate splicing. Using RNA interference (RNAi) in Caenorhabditis elegans, we determined whether interactions between SRm160 and the cleavage machinery are important in a whole organism context. Simultaneous RNAi of SRm160 and the cleavage factor CstF-50 (Cleavage stimulation factor 50-kDa subunit) resulted in late embryonic developmental arrest. In contrast, RNAi of CstF-50 in combination with RNPS1 or REFs did not result in an apparent phenotype. Our combined results provide evidence for an evolutionarily conserved interaction between SRm160 and the 3'-end cleavage machinery that functions independently of EJC formation. (+info)
Developmental distribution of the polyadenylation protein CstF-64 and the variant tauCstF-64 in mouse and rat testis. (4/39)Messenger RNA polyadenylation is one of the processes that control gene expression in all eukaryotic cells and tissues. In mice, two forms of the regulatory polyadenylation protein CstF-64 are found. The gene Cstf2 on the X chromosome encodes this form, and it is expressed in all somatic tissues. The second form, tauCstF-64 (encoded by the autosomal gene Cstf2t), is expressed in a more limited set of tissues and cell types, largely in meiotic and postmeiotic male germ cells and, to a smaller extent, in brain. We report here that whereas CstF-64 and tauCstF-64 expression in rat tissues resembles their expression in mouse tissues, significant differences also are found. First, unlike in mice, in which CstF-64 was expressed in postmeiotic round and elongating spermatids, rat CstF-64 was absent in those cell types. Second, unlike in mice, tauCstF-64 was expressed at significant levels in rat liver. These differences in expression suggest interesting differences in X-chromosomal gene expression between these two rodent species. (+info)
U1A inhibits cleavage at the immunoglobulin M heavy-chain secretory poly(A) site by binding between the two downstream GU-rich regions. (5/39)The immunoglobulin M heavy-chain locus contains two poly(A) sites which are alternatively expressed during B-cell differentiation. Despite its promoter proximal location, the secretory poly(A) site is not expressed in undifferentiated cells. Crucial to the activation of the secretory poly(A) site during B-cell differentiation are changes in the binding of cleavage stimulatory factor 64K to GU-rich elements downstream of the poly(A) site. What regulates this change is not understood. The secretory poly(A) site contains two downstream GU-rich regions separated by a 29-nucleotide sequence. Both GU-rich regions are necessary for binding of the specific cleavage-polyadenylation complex. We demonstrate here that U1A binds two (AUGCN(1-3)C) motifs within the 29-nucleotide sequence and inhibits the binding of cleavage stimulatory factor 64K and cleavage at the secretory poly(A) site. (+info)
Elevated levels of the 64-kDa cleavage stimulatory factor (CstF-64) in lipopolysaccharide-stimulated macrophages influence gene expression and induce alternative poly(A) site selection. (6/39)Lipopolysaccharide (LPS) activation of murine RAW 264.7 macrophages influences the expression of multiple genes through transcriptional and post-transcriptional mechanisms. We observed a 5-fold increase in CstF-64 expression following LPS treatment of RAW macrophages. The increase in CstF-64 protein was specific in that several other factors involved in 3'-end processing were not affected by LPS stimulation. Activation of RAW macrophages with LPS caused an increase in proximal poly(A) site selection within a reporter mini-gene containing two linked poly(A) sites that occurred concomitant with the increase in CstF-64 expression. Furthermore, forced overexpression of the CstF-64 protein also induced alternative poly(A) site selection on the reporter minigene. Microarray analysis performed on CstF-64 overexpressing RAW macrophages revealed that elevated levels of CstF-64 altered the expression of 51 genes, 14 of which showed similar changes in gene expression with LPS stimulation. Sequence analysis of the 3'-untranslated regions of these 51 genes revealed that over 45% possess multiple putative poly(A) sites. Two of these 51 genes demonstrated alternative polyadenylation under both LPS-stimulating and CstF-64-overexpressing conditions. We concluded that the physiologically increased levels of CstF-64 observed in LPS-stimulated RAW macrophages contribute to the changes in expression and alternative polyadenylation of a number of genes, thus identifying another level of gene regulation that occurs in macrophages activated with LPS. (+info)
Symplekin and multiple other polyadenylation factors participate in 3'-end maturation of histone mRNAs. (7/39)Most metazoan messenger RNAs encoding histones are cleaved, but not polyadenylated at their 3' ends. Processing in mammalian cell extracts requires the U7 small nuclear ribonucleoprotein (U7 snRNP) and an unidentified heat-labile factor (HLF). We describe the identification of a heat-sensitive protein complex whose integrity is required for histone pre-mRNA cleavage. It includes all five subunits of the cleavage and polyadenylation specificity factor (CPSF), two subunits of the cleavage stimulation factor (CstF), and symplekin. Reconstitution experiments reveal that symplekin, previously shown to be necessary for cytoplasmic poly(A) tail elongation and translational activation of mRNAs during Xenopus oocyte maturation, is the essential heat-labile component. Thus, a common molecular machinery contributes to the nuclear maturation of mRNAs both lacking and possessing poly(A), as well as to cytoplasmic poly(A) tail elongation. (+info)
Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline. (8/39)The Drosophila master sex-switch protein Sex-lethal (SXL) regulates the splicing and/or translation of three known targets to mediate somatic sexual differentiation. Genetic studies suggest that additional target(s) of SXL exist, particularly in the female germline. Surprisingly, our detailed molecular characterization of a new potential target of SXL, enhancer of rudimentary (e(r)), reveals that SXL regulates e(r) by a novel mechanism--polyadenylation switching--specifically in the female germline. SXL binds to multiple SXL-binding sites, which include the GU-rich poly(A) enhancer, and competes for the binding of CstF64 in vitro. The SXL-binding sites are able to confer sex-specific poly(A) switching onto an otherwise nonresponsive polyadenylation signal in vivo. The sex-specific poly(A) switching of e(r) provides a means for translational regulation in germ cells. We present a model for the SXL-dependent poly(A) site choice in the female germline. (+info)
The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) defines alcohol use disorder as a maladaptive pattern of alcohol use that leads to clinically significant impairment or distress in at least three of the following areas:
1. Drinking more or for longer than intended.
2. Desire or unsuccessful efforts to cut down or control drinking.
3. Spending a lot of time drinking or recovering from its effects.
4. Craving or strong desire to drink.
5. Drinking interferes with work, school, or home responsibilities.
6. Continuing to drink despite social or personal problems caused by alcohol use.
7. Giving up important activities in order to drink.
8. Drinking in hazardous situations (e.g., while driving).
9. Continued drinking despite physical or psychological problems caused or worsened by alcohol use.
10. Developing tolerance (i.e., needing to drink more to achieve the desired effect).
11. Experiencing withdrawal symptoms when alcohol use is stopped or reduced.
The severity of alcoholism is categorized into three subtypes based on the number of criteria met: mild, moderate, and severe. Treatment for alcoholism typically involves a combination of behavioral interventions (e.g., cognitive-behavioral therapy, motivational interviewing) and medications (e.g., disulfiram, naltrexone, acamprosate) to manage withdrawal symptoms and cravings.
In conclusion, alcoholism is a chronic and often progressive disease characterized by excessive and compulsive consumption of alcohol despite negative consequences to physical and mental health, relationships, and social functioning. The diagnostic criteria for alcoholism include a combination of physiological, behavioral, and subjective symptoms, and treatment typically involves a combination of behavioral interventions and medications to manage withdrawal symptoms and cravings.
Cleavage stimulation factor
Partial cleavage stimulation factor domain
AXL receptor tyrosine kinase
List of MeSH codes (D12.776)
Heparin-binding EGF-like growth factor
Transforming protein RhoA
Eukaryotic translation initiation factor 4 gamma 1
List of MeSH codes (D12.776.157)
Robert Almer Harper
Coagulation factor II receptor
Sterol regulatory element-binding protein 1
Leukotriene B4 receptor 2
Pattern recognition receptor
AP-1 transcription factor
Cadherin-catenin complex in learning and memory
Fibroblast growth factor 23
Tartrate-resistant acid phosphatase
Macrophage colony-stimulating factor
Flap structure-specific endonuclease 1
Actin, cytoplasmic 2
cleavage stimulation factor subunit 1 [Rattus norvegicus] - Protein - NCBI
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Pharos : Target Details - CSTF2
Pharos : Target Details - CSTF3
Mobile genetic elements - online presentation
Cleavage and polyadenylation of pre-mRNA
Pesquisa | Prevenção e Controle de Câncer
NDF-RT Code NDF-RT Name
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SRC family kinases mediate epidermal growth factor receptor ligand cleavage, proliferation, and invasion of head and neck...
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Journal of Veterinary Medical Science
Landon Stuart King, M.D., Professor of Medicine | Johns Hopkins Medicine
Pesquisa | Portal Regional da BVS
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Recombinant Mouse BAFF/BLyS/TNFSF13B Protein 8876-BF-010: R&D Systems
Descriptors in 2013 MeSH. Preferred term only. December 14, 2012
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- 12. hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells. (nih.gov)
- Cleavage stimulation factor subunit 3 (CSTF3 or CstF-77) and crooked neck-like protein 1 (CRNKL1) from mammals. (embl.de)
- Cr(VI) induces hypoxia-inducible factor-1 (HIF-1) activity by specific expression of HIF-1a but not HIF-1a subunit and increases vascular endothelial growth factor (VEGF) expression. (cdc.gov)
- Predicted to be part of mRNA cleavage stimulatin. (nih.gov)
- A RNA-binding protein that stimulates the cleavage of the 3' end of MRNA near the POLYADENYLATION site. (nih.gov)
- It is a heterotrimer of 55-, 64- and 77-kDa subunits and combines with CLEAVAGE STIMULATION FACTOR to form a stable complex with mRNA that directs the 3' cleavage and polyadenylation reaction. (nih.gov)
- 3. Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells. (nih.gov)
- The alpha granules contain hemostatic proteins such as fibrinogen, vWf, and growth factors (eg, platelet-derived growth factor and transforming growth factors). (medscape.com)
- Following fertilization, some proteins (e.g. transcription factor Sp1, TATA-box binding protein, RNA pol-II) are translocated from the cytoplasm to the nucleus. (nih.gov)
- At sufficient cellular cholesterol levels, SREBP is retained as a full-length protein in the endoplasmic reticulum (ER) bound to adaptor proteins SREBP cleavage-activating protein (SCAP) and inhibitory insulin-induced gene (INSIG) ( Brown and Goldstein, 1997 ). (elifesciences.org)
- V(D)J recombination: RAG proteins, repair factors, and regulation. (nih.gov)
- The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. (nih.gov)
- The protein encoded by this gene is one of three (including CSTF1 and CSTF2) cleavage stimulation factors that combine to form the cleavage stimulation factor complex (CSTF). (nih.gov)
- GRP can induce rapid phosphorylation of EGFR and p42/44 mitogen-activated protein kinase (MAPK) activation in part via extracellular release of transforming growth factor alpha (TGF-alpha) by matrix metalloproteinases (MMPs). (nih.gov)
- NF-κB, along with other activated transcription factors, such as activator protein 1 (AP1) upregulate the transcription of several inflammatory response genes that increase (1) vascular permeability, (2) leukocyte chemoattraction, and (3) immune cell adhesion and extravasation into tissue ( Pober and Sessa, 2007 ). (elifesciences.org)
- Cellular lipid and cholesterol homeostasis are tightly regulated by the transcription factor sterol response element binding protein (SREBP). (elifesciences.org)
- Inhibition of NF-EB by IKKa-KM or IKKa deficiency results in spontaneous cleavage of Bcl-xL antiapoptotic protein due to elevated caspase-3 activity. (cdc.gov)
- In human leukocytes, and more specifically neutrophils, AMPKα cleavage yields 55- and 35-kDa protein fragments. (nih.gov)
- factor, Smac (second mitochondria derived activator of caspase)/DIABLO (direct inhibitor of apoptosis protein (IAP)-binding protein), Omi/HtrA2, or endonuclease G from the mitochondrial inter-membrane space ( Cande et al. (aktinhibitor.com)
- AR inhibition selects promoter-distal polyadenylation sites (pAs) enriched in cis-elements recognized by the cleavage and polyadenylation specificity factor (CPSF) complex. (bvsalud.org)
- Mechanistically, inflammatory activation of SREBP was mediated by a reduction in accessible cholesterol, leading to heightened sterol sensing and downstream SREBP2 cleavage. (elifesciences.org)
- SRC family kinases mediate epidermal growth factor receptor ligand cleavage, proliferation, and invasion of head and neck cancer cells. (nih.gov)
- B-cell activating factor (BAFF), also known as BLyS, TALL-1, THANK, and TNFSF13B, is a 32 kDa transmembrane glycoprotein in the TNF ligand superfamily. (rndsystems.com)
- We previously reported that both TNFα and IL-1β, which are released by macrophages upon LPS stimulation, affect Fas ligand (FasL)-induced apoptotic signaling. (frontiersin.org)
- Genes down-regulated in comparison of dendritic cells (DC) at 4 h after LPS (TLR4 agonist) stimulation versus those at 16 h after the stimulation. (gsea-msigdb.org)
- Proteolytic Cleavage of AMPKα and Intracellular MMP9 Expression Are Both Required for TLR4-Mediated mTORC1 Activation and HIF-1α Expression in Leukocytes. (nih.gov)
- LPS-induced TLR4 activation alters cellular bioenergetics and triggers proteolytic cleavage of AMPKα and HIF-1α expression in leukocytes. (nih.gov)
- In the liver, LPS leads to the activation of Kupffer cells, the liver resident macrophages, via stimulation of the Toll-like receptor 4 (TLR4) and the induction of an inflammatory response contributing to the progression of alcoholic liver disease ( Seki and Schnabl, 2012 ). (frontiersin.org)
- Stimulation of death receptors results in activation of the initiator caspase-8 which can propagate the apoptotic signal by direct cleavage of downstream effectors such as caspase-3 (Walczak and Krammer, 2000). (aktinhibitor.com)
- Soluble BAFF is stored intracellularly in neutrophils and released upon inflammatory stimulation (6). (rndsystems.com)
- In differentiated cells, a TATA box is required for enhancer-mediated stimulation of promoters, but in undifferentiated cells (for example, mouse cleavage-stage embryos), a TATA box is dispensable and enhancer stimulation is mediated via an Sp1 site. (nih.gov)
- During development, this arrangement allows early enhancer-mediated stimulation of essential promoters that lack a TATA box--such as those governing housekeeping genes--while reducing stimulation later on. (nih.gov)
- One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. (nih.gov)
- Our data indicate that AMPKα cleavage is linked to MMP9 expression and that both are required for mammalian target of rapamycin complex-1 and S6K1 activation and HIF-1α expression in LPS-stimulated human and mice leukocytes. (nih.gov)
- We have identified specific regulatory sequences and transcription factors that are used at the very beginning of mammalian development, and we have uncovered several novel features of zygotic gene activation (ZGA), including: 1) A biological clock delays both initiation of transcription and translation of nascent transcripts until it is time for ZGA. (nih.gov)
- We now aim to identify the roles of specific transcription factors and chromosomal changes in activating key genes at the start of mammalian development. (nih.gov)
- Endothelial cells (ECs) rapidly respond to extrinsic signals, such as tissue damage or microbial infection, by upregulating factors to activate and recruit circulating leukocytes to the site of injury and aberrant activation of ECs leads to inflammatory based diseases, such as multiple sclerosis and atherosclerosis. (elifesciences.org)
- Treatment of primary human ECs with pro-inflammatory cytokines upregulated SREBP2 cleavage and cholesterol biosynthetic gene expression within the late phase of the acute inflammatory response. (elifesciences.org)
- Direct stimulation of vascular smooth muscle cells, in the absence of neuronal activation, similarly enhances glymphatic flow. (nature.com)
- It contains synthetic human Endothelin-1 and antibodies raised against the synthetic factor. (bio-techne.com)
- However, when TNFα action was blocked by neutralizing antibodies, cell viability after stimulation with the BMDM supernatant and FasL increased as compared to single FasL stimulation. (frontiersin.org)
- Brain-derived neurotrophic factor (BDNF) is decreased by 3 to 4-fold in the brains of AD patients at autopsy. (biomedcentral.com)
- Brain-derived neurotrophic factor (BDNF) is a critical factor in synaptic repair and plasticity. (biomedcentral.com)
- We show that, in mice, psychedelics bind directly to TrkB (the brain-derived neurotrophic factor (BDNF) receptor) with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding. (nature.com)
- This cleavage event is rapidly followed by the second S-phase and expression of a small number of zygotic genes (~38 to 282). (nih.gov)
- These techniques revealed that oocytes and preimplantation embryos have the capacity to use specific cis -acting sequences and trans -acting factors to express genes or replicate DNA. (nih.gov)
- The hemostatic system consists of platelets, coagulation factors, and the endothelial cells lining the blood vessels. (medscape.com)
- Fertilization activates the first of six to seven cell cleavage cycles over a four day period that culminate in formation of a blastocyst containing 64 to 128 cells comprising two cell types (Fig. 1). (nih.gov)
- Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. (osti.gov)
- Second, rMMP9 cleaved human AMPKα ex vivo, producing degradation products similar in size to those detected following LPS stimulation. (nih.gov)
- Intracranial stimulation during sleep using prefrontal electric pulses, precisely timed with slow-wave activities in the medial temporal lobe, enhanced the coupling of neuronal oscillations across regions of the human brain and improved memory performance. (nature.com)
- performed real-time closed-loop intracranial stimulation in human sleep. (nature.com)
- Head and neck squamous cell carcinomas (HNSCCs) are characterized by up-regulation of the epidermal growth factor receptor (EGFR). (nih.gov)
- Keratinocyte growth factor modulates alveolar epithelial cell phenotype in vitro: expression of aquaporin-5 (AQP5). (hopkinsmedicine.org)
- Under physiological circumstances, the resistance of the endothelial cell lining to interactions with platelets and coagulation factors prevents thrombosis. (medscape.com)
- A reduced NF-κB activation model was established to further investigate the molecular mechanisms which determine the distinct cell fate decisions after IL-1β and TNFα stimulation. (frontiersin.org)
- In addition, TEAD-2, a transcription factor that can activate enhancers in preimplantation embryos, is first expressed at ZGA. (nih.gov)
- These results suggest that Src family kinases contribute to GRP-mediated EGFR growth and invasion pathways by facilitating cleavage and release of TGF-alpha and amphiregulin in HNSCC. (nih.gov)
- Herein, we uncover a new role for the AR in alternative cleavage and polyadenylation (APA). (bvsalud.org)
- The discovery of the apolipoprotein E (ApoE) 4 allele as a major risk factor for sporadic and late-onset familial AD has brought attention to the possible role of ApoE in neurodegenerative conditions. (biomedcentral.com)
- Apolipoprotein E4 (ApoE4) is a major genetic risk factor for sporadic or late onset Alzheimer's disease (AD). (biomedcentral.com)