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Mol Cell. 2017 Dec 7;68(5):993-1005.e9. doi: 10.1016/j.molcel.2017.10.019. Epub 2017 Nov 5.

Base-Resolution Mapping Reveals Distinct m1A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts.

Author information

1
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
2
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
3
Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
4
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
5
Institute of Molecular Medicine, Peking University, Beijing 100871, China.
6
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Institute of Molecular Medicine, Peking University, Beijing 100871, China.
7
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
8
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: chengqi.yi@pku.edu.cn.

Abstract

Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N1-methyladenosine (m1A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m1A profiling method, based on m1A-induced misincorporation during reverse transcription, and report distinct classes of m1A methylome in the human transcriptome. m1A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency. A different, small subset of m1A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome, and are dependent on the methyltransferase TRMT6/61A. Additionally, we show that m1A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m1A level via TRMT61B, a mitochondria-localizing m1A methyltransferase, demonstrates that m1A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m1A methylome and provide a resource for functional studies of m1A-mediated epitranscriptomic regulation.

KEYWORDS:

N(1)-methyladenosine; RNA epigenetics; RNA modification; base-resolution; epitranscriptomics; m(1)A; mitochondria; translation regulation

PMID:
29107537
PMCID:
PMC5722686
DOI:
10.1016/j.molcel.2017.10.019
[Indexed for MEDLINE]
Free PMC Article

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