Alternative transcription start site selection leads to large differences in translation activity in yeast
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RNA-2012-Rojas-Duran-2299-305.pdf
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1.14 MB
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Author(s) •
Gilbert, Wendy
Rojas Duran, Maria Fernanda
Date Issued
October 2012
Journal
RNA
Publisher
Cold Spring Harbor Laboratory Press
Citation
Rojas-Duran, M. F., and W. V. Gilbert. “Alternative Transcription Start Site Selection Leads to Large Differences in Translation Activity in Yeast.” RNA 18, no. 12 (December 1, 2012): 2299–2305.
Version
Final published version
Abstract
mRNA levels do not accurately predict protein levels in eukaryotic cells. To investigate contributions of 5′ untranslated regions (5′ UTRs) to mRNA-specific differences in translation, we determined the 5′ UTR boundaries of 96 yeast genes for which in vivo translational efficiency varied by 80-fold. A total of 25% of genes showed substantial 5′ UTR heterogeneity. We compared the capacity of these genes' alternative 5′ UTR isoforms for cap-dependent and cap-independent translation using quantitative in vitro and in vivo translation assays. Six out of nine genes showed mRNA isoform-specific translation activity differences of greater than threefold in at least one condition. For three genes, in vivo translation activities of alternative 5′ UTR isoforms differed by more than 100-fold. These results show that changing genes' 5′ UTR boundaries can produce large changes in protein output without changing the overall amount of mRNA. Because transcription start site (TSS) heterogeneity is common, we suggest that TSS choice is greatly under-appreciated as a quantitatively significant mechanism for regulating protein production.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Non-Commercial 3.0 (CC-BY-NC)
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DOI of Published Version
https://doi.org/10.1261/rna.035865.112