The Mammalian Cap-Specific m6Am RNA Methyltransferase PCIF1 Regulates Transcript Levels in Mouse Tissues

被引:58
|
作者
Pandey, Radha Raman [1 ]
Delfino, Elena [1 ]
Homolka, David [1 ]
Roithova, Adriana [1 ]
Chen, Kuan-Ming [1 ]
Li, Lingyun [1 ]
Franco, Giulia [2 ]
Vagbo, Cathrine Broberg [3 ,4 ]
Taillebourg, Emmanuel [2 ]
Fauvarque, Marie-Odile [2 ]
Pillai, Ramesh S. [1 ]
机构
[1] Univ Geneva, Dept Mol Biol, Sci 3, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland
[2] Univ Grenoble Alpes, BGE, INSERM, CEA, F-38000 Grenoble, France
[3] Norwegian Univ Sci & Technol NTNU, Dept Clin & Mol Med, Prote & Mod Expt Core PROMEC, Trondheim, Norway
[4] St Olays Hosp Cent Staff, Trondheim, Norway
来源
CELL REPORTS | 2020年 / 32卷 / 07期
基金
瑞士国家科学基金会;
关键词
MESSENGER-RNA; STRUCTURAL BASIS; GENE-EXPRESSION; POLYMERASE-II; NUCLEAR-RNA; PROTEIN; CELL; METHYLATION; PSEUDOGENES; GENOME;
D O I
10.1016/j.celrep.2020.108038
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The 5' end of eukaryotic mRNAs is protected by the m(7)G-cap structure. The transcription start site nucleotide is ribose methylated (Nm) in many eukaryotes, whereas an adenosine at this position is further methylated at the N-6 position (m(6)A) by the mammalian Phosphorylated C-terminal domain (CTD)-interacting Factor 1 (PCIF1) to generate m(6)Am. Here, we show that although the loss of cap-specific m(6)Am in mice does not affect viability or fertility, the Pcif1 mutants display reduced body weight. Transcriptome analyses of mutant mouse tissues support a role for the cap-specific m(6)Am modification in stabilizing transcripts. In contrast, the Drosophila Pcif1 is catalytically dead, but like its mammalian counterpart, it retains the ability to associate with the Ser5-phosphorylated CTD of RNA polymerase II (RNA Pol II). Finally, we show that the Trypanosoma Pcif1 is an m(6)Am methylase that contributes to the N-6,N-6,2'-O-trimethyladenosine (m(2)(6)Am) in the hypermethylated cap4 structure of trypanosomatids. Thus, PCIF1 has evolved to function in catalytic and non-catalytic roles.
引用
收藏
页数:26
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