Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq

Dan Dominissini, Sharon Moshitch-Moshkovitz, Schraga Schwartz, Mali Salmon-Divon, Lior Ungar, Sivan Osenberg, Karen Cesarkas, Jasmine Jacob-Hirsch, Ninette Amariglio, Martin Kupiec, Rotem Sorek and Gideon Rechavi ()
Additional contact information
Dan Dominissini: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Sharon Moshitch-Moshkovitz: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Schraga Schwartz: Weizmann Institute of Science, Rehovot 76100, Israel
Mali Salmon-Divon: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Lior Ungar: Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Sivan Osenberg: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Karen Cesarkas: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Jasmine Jacob-Hirsch: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Ninette Amariglio: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
Martin Kupiec: Tel Aviv University, Tel Aviv 69978, Israel
Rotem Sorek: Weizmann Institute of Science, Rehovot 76100, Israel
Gideon Rechavi: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel

Nature, 2012, vol. 485, issue 7397, 201-206

Abstract: 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.

Date: 2012
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DOI: 10.1038/nature11112

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