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A periodic pattern of mRNA secondary structure created by the genetic code

Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico a...

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Detalles Bibliográficos
Autores principales: Shabalina, Svetlana A., Ogurtsov, Aleksey Y., Spiridonov, Nikolay A.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458515/
https://www.ncbi.nlm.nih.gov/pubmed/16682450
http://dx.doi.org/10.1093/nar/gkl287
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author Shabalina, Svetlana A.
Ogurtsov, Aleksey Y.
Spiridonov, Nikolay A.
author_facet Shabalina, Svetlana A.
Ogurtsov, Aleksey Y.
Spiridonov, Nikolay A.
author_sort Shabalina, Svetlana A.
collection PubMed
description Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleotide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both protein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA secondary structure, which is likely to be important for transcript stability and translation. We also demonstrate that functional domains of the mRNA [5′-untranslated region (5′-UTR), CDS and 3′-UTR] preferentially fold onto themselves, while the start codon and stop codon regions are characterized by relaxed secondary structures, which may facilitate initiation and termination of translation.
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spelling pubmed-14585152006-05-12 A periodic pattern of mRNA secondary structure created by the genetic code Shabalina, Svetlana A. Ogurtsov, Aleksey Y. Spiridonov, Nikolay A. Nucleic Acids Res Article Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleotide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both protein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA secondary structure, which is likely to be important for transcript stability and translation. We also demonstrate that functional domains of the mRNA [5′-untranslated region (5′-UTR), CDS and 3′-UTR] preferentially fold onto themselves, while the start codon and stop codon regions are characterized by relaxed secondary structures, which may facilitate initiation and termination of translation. Oxford University Press 2006 2006-05-08 /pmc/articles/PMC1458515/ /pubmed/16682450 http://dx.doi.org/10.1093/nar/gkl287 Text en © The Author 2006. Published by Oxford University Press. All rights reserved
spellingShingle Article
Shabalina, Svetlana A.
Ogurtsov, Aleksey Y.
Spiridonov, Nikolay A.
A periodic pattern of mRNA secondary structure created by the genetic code
title A periodic pattern of mRNA secondary structure created by the genetic code
title_full A periodic pattern of mRNA secondary structure created by the genetic code
title_fullStr A periodic pattern of mRNA secondary structure created by the genetic code
title_full_unstemmed A periodic pattern of mRNA secondary structure created by the genetic code
title_short A periodic pattern of mRNA secondary structure created by the genetic code
title_sort periodic pattern of mrna secondary structure created by the genetic code
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458515/
https://www.ncbi.nlm.nih.gov/pubmed/16682450
http://dx.doi.org/10.1093/nar/gkl287
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