Role of mRNA structure in the control of protein folding
Guilhem Faure, Aleksey Y. Ogurtsov, Svetlana A. Shabalina and Eugene V. Koonin*
- Author Affiliations
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
↵*To whom correspondence should be addressed. Tel: +1 301 435 5913; Fax: +1 301 435 7793; Email: koonin@ncbi.nlm.nih.gov
Received May 3, 2016. Revision received July 12, 2016. Accepted July 14, 2016.
Source/Fonte: ISaude
Abstract
Specific structures in mRNA modulate translation rate and thus can affect protein folding. Using the protein structures from two eukaryotes and three prokaryotes, we explore the connections between the protein compactness, inferred from solvent accessibility, and mRNA structure, inferred from mRNA folding energy (ΔG). In both prokaryotes and eukaryotes, the ΔG value of the most stable 30 nucleotide segment of the mRNA (ΔGmin) strongly, positively correlates with protein solvent accessibility. Thus, mRNAs containing exceptionally stable secondary structure elements typically encode compact proteins. The correlations between ΔG and protein compactness are much more pronounced in predicted ordered parts of proteins compared to the predicted disordered parts, indicative of an important role of mRNA secondary structure elements in the control of protein folding. Additionally, ΔG correlates with the mRNA length and the evolutionary rate of synonymous positions. The correlations are partially independent and were used to construct multiple regression models which explain about half of the variance of protein solvent accessibility. These findings suggest a model in which the mRNA structure, particularly exceptionally stable RNA structural elements, act as gauges of protein co-translational folding by reducing ribosome speed when the nascent peptide needs time to form and optimize the core structure.
Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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