Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Identifieur interne : 002301 ( Main/Exploration ); précédent : 002300; suivant : 002302Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Auteurs : Dan Dominissini [Israël] ; Sharon Moshitch-Moshkovitz [Israël] ; Schraga Schwartz [Israël, États-Unis] ; Mali Salmon-Divon [Israël] ; Lior Ungar [Israël] ; Sivan Osenberg [Israël] ; Karen Cesarkas [Israël] ; Jasmine Jacob-Hirsch [Israël] ; Ninette Amariglio [Israël] ; Martin Kupiec [Israël] ; Rotem Sorek [Israël] ; Gideon Rechavi [Israël]Source :
- Nature [ 0028-0836 ] ; 2012-05-10.
Abstract
An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m6A modification landscape in a transcriptome-wide manner, using a novel approach, m6A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m6A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks—around stop codons and within long internal exons—and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m6A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m6A has a fundamental role in regulation of gene expression.
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DOI: 10.1038/nature11112
Affiliations:
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52621</wicri:regionArea><wicri:noRegion>Tel Hashomer 52621</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Israël</country><wicri:regionArea>Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978</wicri:regionArea><wicri:noRegion>Tel Aviv 69978</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Israël</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Nature</title><idno type="ISSN">0028-0836</idno><idno type="eISSN">1476-4687</idno><imprint><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><date when="2012-05-10">2012-05-10</date><biblScope unit="vol">485</biblScope><biblScope unit="issue">7397</biblScope><biblScope unit="page" from="201">201</biblScope><biblScope unit="page" to="206">206</biblScope><date type="Copyright" when="2012">2012</date></imprint><idno type="ISSN">0028-0836</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0028-0836</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m6A modification landscape in a transcriptome-wide manner, using a novel approach, m6A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m6A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks—around stop codons and within long internal exons—and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m6A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m6A has a fundamental role in regulation of gene expression.</div></front></TEI><affiliations><list><country><li>Israël</li><li>États-Unis</li></country></list><tree><country name="Israël"><noRegion><name sortKey="Dominissini, Dan" sort="Dominissini, Dan" uniqKey="Dominissini D" first="Dan" last="Dominissini">Dan Dominissini</name></noRegion><name sortKey="Amariglio, Ninette" sort="Amariglio, Ninette" uniqKey="Amariglio N" first="Ninette" last="Amariglio">Ninette Amariglio</name><name sortKey="Cesarkas, Karen" sort="Cesarkas, Karen" uniqKey="Cesarkas K" first="Karen" last="Cesarkas">Karen Cesarkas</name><name sortKey="Dominissini, Dan" sort="Dominissini, Dan" uniqKey="Dominissini D" first="Dan" last="Dominissini">Dan Dominissini</name><name sortKey="Jacob Hirsch, Jasmine" sort="Jacob Hirsch, Jasmine" uniqKey="Jacob Hirsch J" first="Jasmine" last="Jacob-Hirsch">Jasmine Jacob-Hirsch</name><name sortKey="Kupiec, Martin" sort="Kupiec, Martin" uniqKey="Kupiec M" first="Martin" last="Kupiec">Martin Kupiec</name><name sortKey="Moshitch Moshkovitz, Sharon" sort="Moshitch Moshkovitz, Sharon" uniqKey="Moshitch Moshkovitz S" first="Sharon" last="Moshitch-Moshkovitz">Sharon Moshitch-Moshkovitz</name><name sortKey="Osenberg, Sivan" sort="Osenberg, Sivan" uniqKey="Osenberg S" first="Sivan" last="Osenberg">Sivan Osenberg</name><name sortKey="Osenberg, Sivan" sort="Osenberg, Sivan" uniqKey="Osenberg S" first="Sivan" last="Osenberg">Sivan Osenberg</name><name sortKey="Rechavi, Gideon" sort="Rechavi, Gideon" uniqKey="Rechavi G" first="Gideon" last="Rechavi">Gideon Rechavi</name><name sortKey="Rechavi, Gideon" sort="Rechavi, Gideon" uniqKey="Rechavi G" first="Gideon" last="Rechavi">Gideon Rechavi</name><name sortKey="Rechavi, Gideon" sort="Rechavi, Gideon" uniqKey="Rechavi G" first="Gideon" last="Rechavi">Gideon Rechavi</name><name sortKey="Salmon Divon, Mali" sort="Salmon Divon, Mali" uniqKey="Salmon Divon M" first="Mali" last="Salmon-Divon">Mali Salmon-Divon</name><name sortKey="Schwartz, Schraga" sort="Schwartz, Schraga" uniqKey="Schwartz S" first="Schraga" last="Schwartz">Schraga Schwartz</name><name sortKey="Sorek, Rotem" sort="Sorek, Rotem" uniqKey="Sorek R" first="Rotem" last="Sorek">Rotem Sorek</name><name sortKey="Ungar, Lior" sort="Ungar, Lior" uniqKey="Ungar L" first="Lior" last="Ungar">Lior Ungar</name><name sortKey="Ungar, Lior" sort="Ungar, Lior" uniqKey="Ungar L" first="Lior" last="Ungar">Lior Ungar</name></country><country name="États-Unis"><noRegion><name sortKey="Schwartz, Schraga" sort="Schwartz, Schraga" uniqKey="Schwartz S" first="Schraga" last="Schwartz">Schraga Schwartz</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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