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Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
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Dacheux, Estelle, Malys, Naglis, Meng, Xiang, Ramachandran, Vinoy, Mendes, Pedro and McCarthy, John E. G. (2017) Translation initiation events on structured eukaryotic mRNAs generate gene expression noise. Nucleic Acids Research, 45 (11). pp. 6981-6992. doi:10.1093/nar/gkx430 ISSN 0305-1048.
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Official URL: http://dx.doi.org/10.1093/nar/gkx430
Abstract
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem–loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise. The noise-enhancing effect of the stem–loop structure also remains operational when combined with an upstream open reading frame. This has broad significance, since these elements are known to modulate the expression of a diversity of eukaryotic genes. Our findings suggest a mechanism for posttranscriptional noise generation that will contribute to understanding of the generally poor correlation between protein-level stochasticity and transcriptional bursting. We propose that posttranscriptional stochasticity can be linked to cycles of folding/unfolding of a stem–loop structure, or to interconversion between higher-order structural conformations of a G-rich motif, and have created a correspondingly configured computational model that generates fits to the experimental data. Stochastic events occurring during the ribosomal scanning process can therefore feature alongside transcriptional bursting as a source of noise.
| Item Type: | Journal Article | ||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Gene expression, Gene expression--Noise, Messenger RNA | ||||||||||||||||||
| Journal or Publication Title: | Nucleic Acids Research | ||||||||||||||||||
| Publisher: | Oxford University Press | ||||||||||||||||||
| ISSN: | 0305-1048 | ||||||||||||||||||
| Official Date: | 17 May 2017 | ||||||||||||||||||
| Dates: |
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| Volume: | 45 | ||||||||||||||||||
| Number: | 11 | ||||||||||||||||||
| Page Range: | pp. 6981-6992 | ||||||||||||||||||
| DOI: | 10.1093/nar/gkx430 | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
| Date of first compliant deposit: | 31 May 2017 | ||||||||||||||||||
| Date of first compliant Open Access: | 31 May 2017 | ||||||||||||||||||
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), National Institutes of Health (U.S.) (NIH), National Institute of General Medical Sciences (U.S.) (NIGMS) | ||||||||||||||||||
| Grant number: | BB/1008349/1 (BBSRC), BB/1020535/1 (BBSRC), BB/M017982/1 (BBSRC), GM080219 (NIH/NIGMS) | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
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