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Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts

Xiaoyu Li, Xushen Xiong, Meiling Zhang, Kun Wang, Ying Chen, Jun Zhou, Yuanhui Mao, Jia Lv, Danyang Yi, Xiao-Wei Chen, Chu Wang, Shu-Bing Qian, Chengqi Yi
doi: https://doi.org/10.1101/202747
Xiaoyu Li
1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
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Xushen Xiong
1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
2Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, PR China
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Meiling Zhang
1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
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Kun Wang
1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
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Ying Chen
3Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
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Jun Zhou
4Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
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Yuanhui Mao
4Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
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Jia Lv
5Institute of Molecular Medicine, Peking University, Beijing, China
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Danyang Yi
1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
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Xiao-Wei Chen
5Institute of Molecular Medicine, Peking University, Beijing, China
6Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
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Chu Wang
3Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
6Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
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Shu-Bing Qian
4Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
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Chengqi Yi
1State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
3Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
6Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
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  • For correspondence: chengqi.yi@pku.edu.cn
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SUMMARY

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, regulation and function. 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 first nucleotide of mRNA, associate with increased translation efficiency. A different 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 for the first time 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.

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Posted October 13, 2017.
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Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts
Xiaoyu Li, Xushen Xiong, Meiling Zhang, Kun Wang, Ying Chen, Jun Zhou, Yuanhui Mao, Jia Lv, Danyang Yi, Xiao-Wei Chen, Chu Wang, Shu-Bing Qian, Chengqi Yi
bioRxiv 202747; doi: https://doi.org/10.1101/202747
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Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts
Xiaoyu Li, Xushen Xiong, Meiling Zhang, Kun Wang, Ying Chen, Jun Zhou, Yuanhui Mao, Jia Lv, Danyang Yi, Xiao-Wei Chen, Chu Wang, Shu-Bing Qian, Chengqi Yi
bioRxiv 202747; doi: https://doi.org/10.1101/202747

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