A general strategy to inhibiting viral −1 frameshifting based on upstream attenuation duplex formation
Identifieur interne : 001922 ( Main/Exploration ); précédent : 001921; suivant : 001923A general strategy to inhibiting viral −1 frameshifting based on upstream attenuation duplex formation
Auteurs : Hao-Teng Hu ; Che-Pei Cho ; Ya-Hui Lin ; Kung-Yao ChangSource :
- Nucleic Acids Research [ 0305-1048 ] ; 2015.
Descripteurs français
- KwdFr :
- ADN (génétique), ADN (métabolisme), ADN antisens (génétique), ADN antisens (métabolisme), ARN messager (génétique), ARN viral (), ARN viral (génétique), ARN viral (métabolisme), Cellules HEK293, Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Décalage ribosomique du cadre de lecture, Humains, Lignée cellulaire, Ribosomes (métabolisme), Régulation de l'expression des gènes viraux, Séquences répétées inversées.
- MESH :
- génétique : ADN, ADN antisens, ARN messager, ARN viral, Coronavirus du syndrome respiratoire du Moyen-Orient.
- métabolisme : ADN, ADN antisens, ARN viral, Coronavirus du syndrome respiratoire du Moyen-Orient, Ribosomes.
- ARN viral, Cellules HEK293, Décalage ribosomique du cadre de lecture, Humains, Lignée cellulaire, Régulation de l'expression des gènes viraux, Séquences répétées inversées.
English descriptors
- KwdEn :
- Cell Line, DNA (genetics), DNA (metabolism), DNA, Antisense (genetics), DNA, Antisense (metabolism), Frameshifting, Ribosomal, Gene Expression Regulation, Viral, HEK293 Cells, Humans, Inverted Repeat Sequences, Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (metabolism), RNA, Messenger (genetics), RNA, Viral (chemistry), RNA, Viral (genetics), RNA, Viral (metabolism), Ribosomes (metabolism).
- MESH :
- chemical , chemistry : RNA, Viral.
- chemical , genetics : DNA, DNA, Antisense, RNA, Messenger, RNA, Viral.
- chemical , metabolism : DNA, DNA, Antisense, RNA, Viral.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- metabolism : Middle East Respiratory Syndrome Coronavirus, Ribosomes.
- Cell Line, Frameshifting, Ribosomal, Gene Expression Regulation, Viral, HEK293 Cells, Humans, Inverted Repeat Sequences.
Abstract
Viral −1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on −1 PRF for optimal propagation. Efficient eukaryotic −1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral −1 PRF stimulators have been developed. However, accessing particular −1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate −1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate −1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for −1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates −1 PRF stimulated by distinct −1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral −1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.
Url:
DOI: 10.1093/nar/gkv1307
PubMed: 26612863
PubMed Central: 4705660
Affiliations:
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Le document en format XML
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sort="Chang, Kung Yao" uniqKey="Chang K" first="Kung-Yao" last="Chang">Kung-Yao Chang</name></author></analytic><series><title level="j">Nucleic Acids Research</title><idno type="ISSN">0305-1048</idno><idno type="eISSN">1362-4962</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line</term><term>DNA (genetics)</term><term>DNA (metabolism)</term><term>DNA, Antisense (genetics)</term><term>DNA, Antisense (metabolism)</term><term>Frameshifting, Ribosomal</term><term>Gene Expression Regulation, Viral</term><term>HEK293 Cells</term><term>Humans</term><term>Inverted Repeat Sequences</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term><term>RNA, Messenger (genetics)</term><term>RNA, Viral (chemistry)</term><term>RNA, Viral (genetics)</term><term>RNA, Viral (metabolism)</term><term>Ribosomes (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (génétique)</term><term>ADN (métabolisme)</term><term>ADN antisens (génétique)</term><term>ADN antisens (métabolisme)</term><term>ARN messager (génétique)</term><term>ARN viral ()</term><term>ARN viral (génétique)</term><term>ARN viral (métabolisme)</term><term>Cellules HEK293</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term><term>Décalage ribosomique du cadre de lecture</term><term>Humains</term><term>Lignée cellulaire</term><term>Ribosomes (métabolisme)</term><term>Régulation de l'expression des gènes viraux</term><term>Séquences répétées inversées</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>DNA</term><term>DNA, Antisense</term><term>RNA, Messenger</term><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA</term><term>DNA, Antisense</term><term>RNA, Viral</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN</term><term>ADN antisens</term><term>ARN messager</term><term>ARN viral</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Ribosomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ADN</term><term>ADN antisens</term><term>ARN viral</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Ribosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Frameshifting, Ribosomal</term><term>Gene Expression Regulation, Viral</term><term>HEK293 Cells</term><term>Humans</term><term>Inverted Repeat Sequences</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN viral</term><term>Cellules HEK293</term><term>Décalage ribosomique du cadre de lecture</term><term>Humains</term><term>Lignée cellulaire</term><term>Régulation de l'expression des gènes viraux</term><term>Séquences répétées inversées</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>Viral −1 programmed ribosomal frameshifting (PRF) as a potential antiviral target has attracted interest because many human viral pathogens, including human immunodeficiency virus (HIV) and coronaviruses, rely on −1 PRF for optimal propagation. Efficient eukaryotic −1 PRF requires an optimally placed stimulator structure downstream of the frameshifting site and different strategies targeting viral −1 PRF stimulators have been developed. However, accessing particular −1 PRF stimulator information represents a bottle-neck in combating the emerging epidemic viral pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, an RNA hairpin upstream of frameshifting site was shown to act as a cis-element to attenuate −1 PRF with mechanism unknown. Here, we show that an upstream duplex formed in-trans, by annealing an antisense to its complementary mRNA sequence upstream of frameshifting site, can replace an upstream hairpin to attenuate −1 PRF efficiently. This finding indicates that the formation of a proximal upstream duplex is the main determining factor responsible for −1 PRF attenuation and provides mechanistic insight. Additionally, the antisense-mediated upstream duplex approach downregulates −1 PRF stimulated by distinct −1 PRF stimulators, including those of MERS-CoV, suggesting its general application potential as a robust means to evaluating viral −1 PRF inhibition as soon as the sequence information of an emerging human coronavirus is available.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Namy, O" uniqKey="Namy O">O. Namy</name></author><author><name sortKey="Rousset, J P" uniqKey="Rousset J">J.P. Rousset</name></author><author><name sortKey="Napthine, S" uniqKey="Napthine S">S. Napthine</name></author><author><name sortKey="Brierley, I" uniqKey="Brierley I">I. Brierley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manktelow, E" uniqKey="Manktelow E">E. Manktelow</name></author><author><name sortKey="Shigemoto, K" uniqKey="Shigemoto K">K. 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Atmar</name></author><author><name sortKey="Peters, C J" uniqKey="Peters C">C.J. Peters</name></author><author><name sortKey="Couch, R B" uniqKey="Couch R">R.B. Couch</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Chang, Kung Yao" sort="Chang, Kung Yao" uniqKey="Chang K" first="Kung-Yao" last="Chang">Kung-Yao Chang</name><name sortKey="Cho, Che Pei" sort="Cho, Che Pei" uniqKey="Cho C" first="Che-Pei" last="Cho">Che-Pei Cho</name><name sortKey="Hu, Hao Teng" sort="Hu, Hao Teng" uniqKey="Hu H" first="Hao-Teng" last="Hu">Hao-Teng Hu</name><name sortKey="Lin, Ya Hui" sort="Lin, Ya Hui" uniqKey="Lin Y" first="Ya-Hui" last="Lin">Ya-Hui Lin</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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