Regulation of programmed ribosomal frameshifting by co-translational refolding RNA hairpins.
Identifieur interne : 002667 ( Ncbi/Curation ); précédent : 002666; suivant : 002668Regulation of programmed ribosomal frameshifting by co-translational refolding RNA hairpins.
Auteurs : Che-Pei Cho [République populaire de Chine] ; Szu-Chieh Lin ; Ming-Yuan Chou ; Hsiu-Ting Hsu ; Kung-Yao ChangSource :
- PloS one [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , chemistry : RNA, Viral.
- chemical , genetics : RNA, Viral.
- genetics : SARS Virus, Saccharomyces cerevisiae.
- Base Pairing, Base Sequence, Frameshifting, Ribosomal, Inverted Repeat Sequences, Nucleotide Motifs, RNA Stability.
Abstract
RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3' direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) -1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate-1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for-1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing-1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study's findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.
DOI: 10.1371/journal.pone.0062283
PubMed: 23638024
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pubmed:23638024Le document en format XML
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sort="Hsu, Hsiu Ting" uniqKey="Hsu H" first="Hsiu-Ting" last="Hsu">Hsiu-Ting Hsu</name></author><author><name sortKey="Chang, Kung Yao" sort="Chang, Kung Yao" uniqKey="Chang K" first="Kung-Yao" last="Chang">Kung-Yao Chang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23638024</idno><idno type="pmid">23638024</idno><idno type="doi">10.1371/journal.pone.0062283</idno><idno type="wicri:Area/PubMed/Corpus">001205</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001205</idno><idno type="wicri:Area/PubMed/Curation">001205</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001205</idno><idno type="wicri:Area/PubMed/Checkpoint">001113</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001113</idno><idno type="wicri:Area/Ncbi/Merge">002667</idno><idno 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Chou</name></author><author><name sortKey="Hsu, Hsiu Ting" sort="Hsu, Hsiu Ting" uniqKey="Hsu H" first="Hsiu-Ting" last="Hsu">Hsiu-Ting Hsu</name></author><author><name sortKey="Chang, Kung Yao" sort="Chang, Kung Yao" uniqKey="Chang K" first="Kung-Yao" last="Chang">Kung-Yao Chang</name></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Pairing</term><term>Base Sequence</term><term>Frameshifting, Ribosomal</term><term>Inverted Repeat Sequences</term><term>Nucleotide Motifs</term><term>RNA Stability</term><term>RNA, Viral (chemistry)</term><term>RNA, Viral (genetics)</term><term>SARS Virus (genetics)</term><term>Saccharomyces cerevisiae (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral ()</term><term>ARN viral (génétique)</term><term>Appariement de bases</term><term>Décalage ribosomique du cadre de lecture</term><term>Motifs nucléotidiques</term><term>Saccharomyces cerevisiae (génétique)</term><term>Stabilité de l'ARN</term><term>Séquence nucléotidique</term><term>Séquences répétées inversées</term><term>Virus du SRAS (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term><term>Saccharomyces cerevisiae</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN viral</term><term>Saccharomyces cerevisiae</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Pairing</term><term>Base Sequence</term><term>Frameshifting, Ribosomal</term><term>Inverted Repeat Sequences</term><term>Nucleotide Motifs</term><term>RNA Stability</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN viral</term><term>Appariement de bases</term><term>Décalage ribosomique du cadre de lecture</term><term>Motifs nucléotidiques</term><term>Stabilité de l'ARN</term><term>Séquence nucléotidique</term><term>Séquences répétées inversées</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3' direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) -1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate-1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for-1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing-1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study's findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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