Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase
| Autor: | Yue Shi, Weiping Yuan, Samir Adhikari, Xiaofan Zhu, Xiao-Min Lou, Xinquan Wang, Ujwal Dahal, Lu Wang, Yong-Liang Zhao, Xin Yang, Jun Huang, Xi Liu, Ang Li, Yun-Gui Yang, Ying Yang, Yu-Sheng Chen, Wenjia Wang, Wen Xiao, Ying Lv, Xu Zhao, Xiao-Li Ping, Jannie M. Rendtlew Danielsen, Bao-Fa Sun, Feng Liu, Tao Cheng |
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| Rok vydání: | 2014 |
| Předmět: |
Embryo
Nonmammalian mRNA Cell Cycle Proteins Biology chemistry.chemical_compound Transcription (biology) RNA interference Animals Humans RNA Messenger RNA Small Interfering Molecular Biology Zebrafish Cell Nucleus Methyltransferase complex Gene Expression Profiling MRNA modification Alternative splicing Nuclear Proteins RNA Cell Differentiation Methyltransferases m6A methyltransferase Cell Biology Molecular biology WTAP Cell biology Alternative Splicing HEK293 Cells Gene Expression Regulation chemistry METTL3 RNA Interference Original Article METTL14 RNA Splicing Factors MRNA methylation N6-Methyladenosine HeLa Cells Protein Binding |
| Zdroj: | Cell Research |
| ISSN: | 1748-7838 1001-0602 |
| Popis: | The methyltransferase like 3 (METTL3)-containing methyltransferase complex catalyzes the N6-methyladenosine (m6A) formation, a novel epitranscriptomic marker; however, the nature of this complex remains largely unknown. Here we report two new components of the human m6A methyltransferase complex, Wilms' tumor 1-associating protein (WTAP) and methyltransferase like 14 (METTL14). WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic activity of the m6A methyltransferase in vivo. The majority of RNAs bound by WTAP and METTL3 in vivo represent mRNAs containing the consensus m6A motif. In the absence of WTAP, the RNA-binding capability of METTL3 is strongly reduced, suggesting that WTAP may function to regulate recruitment of the m6A methyltransferase complex to mRNA targets. Furthermore, transcriptomic analyses in combination with photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) illustrate that WTAP and METTL3 regulate expression and alternative splicing of genes involved in transcription and RNA processing. Morpholino-mediated knockdown targeting WTAP and/or METTL3 in zebrafish embryos caused tissue differentiation defects and increased apoptosis. These findings provide strong evidence that WTAP may function as a regulatory subunit in the m6A methyltransferase complex and play a critical role in epitranscriptomic regulation of RNA metabolism. |
| Databáze: | OpenAIRE |
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