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 N(6)-methyladenosine (m(6)A) 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 m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A 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 m(6)A 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 m(6)A has a fundamental role in regulation of gene expression.
journal_name
Naturejournal_title
Natureauthors
Dominissini D,Moshitch-Moshkovitz S,Schwartz S,Salmon-Divon M,Ungar L,Osenberg S,Cesarkas K,Jacob-Hirsch J,Amariglio N,Kupiec M,Sorek R,Rechavi Gdoi
10.1038/nature11112subject
Has Abstractpub_date
2012-04-29 00:00:00pages
201-6issue
7397eissn
0028-0836issn
1476-4687pii
nature11112journal_volume
485pub_type
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