Title Translation initiation events on structured eukaryotic mRNAs generate gene expression noise /
Authors Dacheux, Estelle ; Malys, Naglis ; Meng, Xiang ; Ramachandran, Vinoy ; Mendes, Pedro ; McCarthy, John E.G
DOI 10.1093/nar/gkx430
Full Text Download
Is Part of Nucleic acids research.. Oxford : Oxford University Press. 2017, vol. 45, iss. 11, p. 6981-6992.. ISSN 0305-1048. eISSN 1362-4962
Keywords [eng] saccharomyces-cerevisiae ; 5-untranslated region ; protein expression ; g-quadruplexes ; reveals ; evolution ; stochasticity ; consequences ; fluctuations ; termination
Abstract [eng] 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.
Published Oxford : Oxford University Press
Type Journal article
Language English
Publication date 2017
CC license CC license description