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.