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M6A-dependent regulation of messenger RNA stability

ABSTRACT: N6-methyladenosine (m6A) is the most prevalent internal modification present in the mRNA of all higher eukaryotes. Here we present that m6A is selectively recognized by human YTH domain family (YTHDF2) protein to regulate mRNA degradation. By using crosslinking and immunoprecipitation, we have identified over 4000 substrate RNA of YTHDF2 with conserved core motif of G(m6A)C. We further estabilshed the role of YTHDF2 in RNA metabolism by a combination of ribosome profiling, RNA sequencing, m6A level quantification and cell-based imaging: the C-terminal domain of YTHDF2 selectively binds to m6A of mRNA and the N-terminal domain is responsive for localizing mRNA from translatable pool to processing body where mRNA decay occurs. PAR-CLIP and RIP was used to identify YTHDF2 binding sites followed by ribosome profling and RNA seq to assess the consequences of YTHDF2 siRNA knock-down

ORGANISM(S): Homo sapiens

SUBMITTER: zhike lu

PROVIDER: E-GEOD-49339 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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N6-methyladenosine-dependent regulation of messenger RNA stability.

Wang Xiao X Lu Zhike Z Gomez Adrian A Hon Gary C GC Yue Yanan Y Han Dali D Fu Ye Y Parisien Marc M Dai Qing Q Jia Guifang G Ren Bing B Pan Tao T He Chuan C

Nature 20131127 7481

N(6)-methyladenosine (m(6)A) is the most prevalent internal (non-cap) modification present in the messenger RNA of all higher eukaryotes. Although essential to cell viability and development, the exact role of m(6)A modification remains to be determined. The recent discovery of two m(6)A demethylases in mammalian cells highlighted the importance of m(6)A in basic biological functions and disease. Here we show that m(6)A is selectively recognized by the human YTH domain family 2 (YTHDF2) 'reader' ...[more]

PMID: 24284625

Publication: 1/2

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