Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Identification and Characterization of the Mammalian Nuclear RNA N6-Adenosine Methyltransferase Core Complex


ABSTRACT: N6-methyladenosine (m6A) is the most prevalent internal modification found in mammalian messenger and non-coding RNAs. The discoveries of functionally significant demethylases that reverse this methylation as well as the recently revealed m6A distributions in mammalian transcriptomes strongly indicate regulatory functions of this modification. Here we report the identification and characterization of the mammalian nuclear RNA N6-adenosine methyltransferase core (RNMTC) complex. Besides METTL3, a methyltransferase which was the only known component of RNMTC in the past, we discovered that a previously uncharacterized methyltransferase, METTL14, exhibits a N6-adenosine methyltransferase activity higher than METTL3. Together with WTAP, the third component that dramatically affects the cellular m6A level, these three proteins form the core complex that orchestrates m6A deposition on mammalian nuclear RNA. Biochemistry assays, imaging experiments, as well as transcriptome-wide analyses of the binding sites and their effects on m6A methylation support methylation function and reveal new insights of RNMTC. PAR-CLIP and m6A-seq in HeLa cells

ORGANISM(S): Homo sapiens

SUBMITTER: Dali Han 

PROVIDER: E-GEOD-46705 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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]

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