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Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is [N.sup.6]-methyladenosine ([m.sup.6]A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, [N.sup.1]-methyladenosine ([m.sup.1]A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that [m.sup.1]A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for [m.sup.1]A in promoting translation of methylated mRNA., Four decades after it was first observed as an abundant constituent of the eukaryotic transcriptome, [m.sup.6]A has only recently been revealed to broadly affect mRNA metabolism (1,2). Consequently, a broader [...]

MicroRNAs (miRNAs) show differential expression across breast cancer subtypes, and have both oncogenic and tumour-suppressive roles (1-6). Here we report the miRNA expression profiles of 1,302 breast tumours with matching [...]

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 ([m.sup.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.sup.6]A modification landscape in a transcriptome-wide manner, using a novel approach,[m.sup.6]A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 [m.sup.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.sup.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.sup.6]A has a fundamental role in regulation of gene expression., Although the multiple layers of epigenetic regulation that result from modification of DNA and proteins have been intensively explored, RNA modifications are still uncharted territory (1). The complex structure--function relationship [...]

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. [ABSTRACT FROM AUTHOR]