Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast
| العنوان: | Cis-regulatory elements explain most of the mRNA stability variation across genes in yeast |
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| المؤلفون: | Kerstin C. Maier, Petra Rus, Žiga Avsec, Jun Cheng, Julien Gagneur |
| المصدر: | RNA |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Genetics, Exonuclease, Untranslated region, Messenger RNA, biology, Three prime untranslated region, Nonsense-mediated decay, Genomics, Computational biology, biology.organism_classification, Genome, Article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Codon usage bias, Schizosaccharomyces pombe, Gene expression, biology.protein, Molecular Biology, Gene, Function (biology), 030217 neurology & neurosurgery |
| الوصف: | The stability of mRNA is one of the major determinants of gene expression. Although a wealth of sequence elements regulating mRNA stability has been described, their quantitative contributions to half-life are unknown. Here, we built a quantitative model for Saccharomyces cerevisiae based on functional mRNA sequence features that explains 60% of the half-life variation between genes and predicts half-life at a median relative error of 30%. The model revealed a new destabilizing 3’UTR motif, ATATTC, which we functionally validated. Codon usage proves to be the major determinant of mRNA stability. Nonetheless, single-nucleotide variations have the largest effect when occurring on 3’UTR motifs or upstream AUGs. Analyzing mRNA half-life data of 34 knockout strains showed that the effect of codon usage not only requires functional decapping and deadenylation, but also the 5’-to-3’ exonuclease Xrn1, the non-sense mediated decay genes, but not no-go decay. Altogether, this study quantitatively delineates the contributions of mRNA sequence features on stability in yeast, reveals their functional dependencies on degradation pathways, and allows accurate prediction of half-life from mRNA sequence. |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| تدمد: | 1469-9001 1355-8382 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9307a126eeb408f0ec4b10f6cada70a https://doi.org/10.1261/rna.062224.117 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b9307a126eeb408f0ec4b10f6cada70a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14699001 13558382 |
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