Moreover, the m6A modification in the C9ORF72 intron sequence upstream of the expanded repeats enhances RNA decay via the nuclear reader YTHDC1, and the antisense RNA repeats can also be regulated through m6A modification. (bvsalud.org)
Overexpression2
Repetitive RNAs and dipeptide repeat proteins are produced by transcription and translation of these repeat expansions and overexpression of these can induce ALS-like pathology 17 . (nature.com)
In Drosophila , ubiquitin proteasome system (UPS) impairment leads to enhancement of CGG-repeat-induced degeneration, whereas overexpression of the chaperone protein HSP70 suppresses this toxicity. (sdbonline.org)
Induce2
Taken together, these findings suggest that CGG repeats induce UPS impairment at least in part through activation of RAN translation (Oh, 2015). (sdbonline.org)
CGG repeats induce impairment of the ubiquitin proteasome system. (sdbonline.org)
C9ORF724
Repeat expansions in C9ORF72, the major cause of ALS, reduce C9ORF72 levels but how this impacts stress granules is uncertain. (nature.com)
Patients with C9ORF72 repeat expansions accumulate symmetric arginine dimethylated proteins which co-localize with p62. (nature.com)
C9ORF72 repeat expansions also cause decreased levels of C9ORF72 mRNA and protein, suggesting that alongside repeat-induced pathology certain aspects of ALS pathology could be caused by loss of C9ORF72 function 18 , 19 . (nature.com)
The earlier finding that CGG repeats support RAN translation to produce homopolymeric proteins containing polyglycine and (in cell culture models) polyalanine suggests one possible mechanism by which this might occur. (sdbonline.org)
RNAs1
The m6A reduction increases the accumulation of repeat RNAs and the encoded poly-dipeptides, contributing to disease pathogenesis. (bvsalud.org)
Patients1
DNA from these patients, as well as 24 additional ALS patients, was genotyped for three TMEM106B single nucleotide polymorphisms known to confer increased risk of FTLD-TDP. (nih.gov)
Translation7
We then focus on ALS-linked genes and discuss the recent progress on how translation is affected by various mutant genes and the repeat expansion-mediated non-canonical translation in ALS. (bvsalud.org)
RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome. (sdbonline.org)
However, recent studies demonstrate that the repeat also elicits production of a toxic polyglycine protein, FMRpolyG, via repeat-associated non-AUG (RAN)-initiated translation. (sdbonline.org)
To delineate the contributions from CGG repeats as RNA from RAN translation-associated toxicity, the production of FMRpolyG in these models was either enhanced or impaired. (sdbonline.org)
Repeat-associated non-AUG (RAN) translation leads to inclusion formation in a Drosophila model of CGG repeat toxicity. (sdbonline.org)
These processes are largely dependent on RAN translation of the CGG repeat into the polyglycine-containing protein, FMRpolyG. (sdbonline.org)
Taken together with previous studies, these findings suggest a model where CGG repeat expansions in FMR1 elicit neuronal proteostasis via RAN translation and contribute to FXTAS pathogenesis (Oh, 2015). (sdbonline.org)
Alterations1
First, it was found that not only are models of FXTAS sensitive to alterations in proteostasis pathways but also that CGG repeat expression is capable of inducing UPS impairment. (sdbonline.org)
Genes1
131 genes were identified in the plastome out of which 113 are unique and 18 were repeated in IR region. (biomedcentral.com)
Accumulation1
In transfected mammalian cells, CGG repeat expression triggers accumulation of a UPS reporter in a length-dependent fashion. (sdbonline.org)