Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.

The initiation of translation is a fundamental and highly regulated process in gene expression. Translation initiation in prokaryotic systems usually requires interaction between the ribosome and an mRNA sequence upstream of the initiation codon, the so-called ribosome-binding site (Shine-Dalgarno s...

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Main Authors: Lars B Scharff, Liam Childs, Dirk Walther, Ralph Bock
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-06-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC3121790?pdf=render
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author Lars B Scharff
Liam Childs
Dirk Walther
Ralph Bock
author_facet Lars B Scharff
Liam Childs
Dirk Walther
Ralph Bock
author_sort Lars B Scharff
collection DOAJ
description The initiation of translation is a fundamental and highly regulated process in gene expression. Translation initiation in prokaryotic systems usually requires interaction between the ribosome and an mRNA sequence upstream of the initiation codon, the so-called ribosome-binding site (Shine-Dalgarno sequence). However, a large number of genes do not possess Shine-Dalgarno sequences, and it is unknown how start codon recognition occurs in these mRNAs. We have performed genome-wide searches in various groups of prokaryotes in order to identify sequence elements and/or RNA secondary structural motifs that could mediate translation initiation in mRNAs lacking Shine-Dalgarno sequences. We find that mRNAs without a Shine-Dalgarno sequence are generally less structured in their translation initiation region and show a minimum of mRNA folding at the start codon. Using reporter gene constructs in bacteria, we also provide experimental support for local RNA unfoldedness determining start codon recognition in Shine-Dalgarno--independent translation. Consistent with this, we show that AUG start codons reside in single-stranded regions, whereas internal AUG codons are usually in structured regions of the mRNA. Taken together, our bioinformatics analyses and experimental data suggest that local absence of RNA secondary structure is necessary and sufficient to initiate Shine-Dalgarno--independent translation. Thus, our results provide a plausible mechanism for how the correct translation initiation site is recognized in the absence of a ribosome-binding site.
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spelling doaj.art-89043296d91e4aa4b73267dc5026d1a62022-12-22T02:06:45ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-06-0176e100215510.1371/journal.pgen.1002155Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.Lars B ScharffLiam ChildsDirk WaltherRalph BockThe initiation of translation is a fundamental and highly regulated process in gene expression. Translation initiation in prokaryotic systems usually requires interaction between the ribosome and an mRNA sequence upstream of the initiation codon, the so-called ribosome-binding site (Shine-Dalgarno sequence). However, a large number of genes do not possess Shine-Dalgarno sequences, and it is unknown how start codon recognition occurs in these mRNAs. We have performed genome-wide searches in various groups of prokaryotes in order to identify sequence elements and/or RNA secondary structural motifs that could mediate translation initiation in mRNAs lacking Shine-Dalgarno sequences. We find that mRNAs without a Shine-Dalgarno sequence are generally less structured in their translation initiation region and show a minimum of mRNA folding at the start codon. Using reporter gene constructs in bacteria, we also provide experimental support for local RNA unfoldedness determining start codon recognition in Shine-Dalgarno--independent translation. Consistent with this, we show that AUG start codons reside in single-stranded regions, whereas internal AUG codons are usually in structured regions of the mRNA. Taken together, our bioinformatics analyses and experimental data suggest that local absence of RNA secondary structure is necessary and sufficient to initiate Shine-Dalgarno--independent translation. Thus, our results provide a plausible mechanism for how the correct translation initiation site is recognized in the absence of a ribosome-binding site.http://europepmc.org/articles/PMC3121790?pdf=render
spellingShingle Lars B Scharff
Liam Childs
Dirk Walther
Ralph Bock
Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.
PLoS Genetics
title Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.
title_full Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.
title_fullStr Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.
title_full_unstemmed Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.
title_short Local absence of secondary structure permits translation of mRNAs that lack ribosome-binding sites.
title_sort local absence of secondary structure permits translation of mrnas that lack ribosome binding sites
url http://europepmc.org/articles/PMC3121790?pdf=render
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