Specificity of mRNA Folding and Its Association with Evolutionarily Adaptive mRNA Secondary Structures.

Genomics Proteomics Bioinformatics

Program in Cancer Research, Zhongshan School of Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address:

Published: December 2021

The secondary structure is a fundamental feature of both non-coding RNAs (ncRNAs) and messenger RNAs (mRNAs). However, our understanding of the secondary structures of mRNAs, especially those of the coding regions, remains elusive, likely due to translation and the lack of RNA-binding proteins that sustain the consensus structure like those binding to ncRNAs. Indeed, mRNAs have recently been found to adopt diverse alternative structures, but the overall functional significance remains untested. We hereby approach this problem by estimating the folding specificity, i.e., the probability that a fragment of an mRNA folds back to the same partner once refolded. We show that the folding specificity of mRNAs is lower than that of ncRNAs and exhibits moderate evolutionary conservation. Notably, we find that specific rather than alternative folding is likely evolutionarily adaptive since specific folding is frequently associated with functionally important genes or sites within a gene. Additional analysis in combination with ribosome density suggests the ability to modulate ribosome movement as one potential functional advantage provided by specific folding. Our findings reveal a novel facet of the RNA structurome with important functional and evolutionary implications and indicate a potential method for distinguishing the mRNA secondary structures maintained by natural selection from molecular noise.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403030PMC
http://dx.doi.org/10.1016/j.gpb.2019.11.013DOI Listing

Publication Analysis

Top Keywords

secondary structures
12
evolutionarily adaptive
8
mrna secondary
8
folding specificity
8
specific folding
8
folding
6
specificity mrna
4
mrna folding
4
folding association
4
association evolutionarily
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!