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Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs

Item Type:Article
Title:Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs
Creators Name:Meyer, I.M. and Miklos, I.
Abstract:Owing to the degeneracy of the genetic code, protein-coding regions of mRNA sequences can harbour more than only amino acid information. We search the mRNA sequences of 11 human protein-coding genes for evolutionarily conserved secondary structure elements using RNA-Decoder, a comparative secondary structure prediction program that is capable of explicitly taking the known protein-coding context of the mRNA sequences into account. We detect well-defined, conserved RNA secondary structure elements in the coding regions of the mRNA sequences and show that base-paired codons strongly correlate with sparse codons. We also investigate the role of repetitive elements in the formation of secondary structure and explain the use of alternate start codons in the caveolin-1 gene by a conserved secondary structure element overlapping the nominal start codon. We discuss the functional roles of our novel findings in regulating the gene expression on mRNA level. We also investigate the role of secondary structure on the correct splicing of the human CFTR gene. We study the wild-type version of the pre-mRNA as well as 29 variants with synonymous mutations in exon 12. By comparing our predicted secondary structures to the experimentally determined splicing efficiencies, we find with weak statistical significance that pre-mRNAs with high-splicing efficiencies have different predicted secondary structures than pre-mRNAs with low-splicing efficiencies.
Keywords:Codon, Computational Biology, Cystic Fibrosis Transmembrane Conductance Regulator, Exons, Gene Expression Regulation, Initiator Codon, Messenger RNA, Molecular Evolution, Nucleic Acid Conformation, Nucleic Acid Repetitive Sequences, RNA Precursors, RNA Splicing, Software, Statistical Data Interpretation, Animals, Cats, Cattle, Dogs, Mice, Rabbits, Rats
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:6338-6348
Date:7 November 2005
Official Publication:https://doi.org/10.1093/nar/gki923
PubMed:View item in PubMed

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