Journal
CELL RESEARCH
Volume 29, Issue 11, Pages 927-941Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41422-019-0230-z
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Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010500]
- National Natural Science Foundation of China [31625016, 31770872]
- CAS Key Research Projects of the Frontier Science [QYZDY-SSW-SMC027]
- National Key Research and Development Program of China, Stem Cell and Translational Research [2018YFA0109700]
- Youth Innovation Promotion Association of CAS [2018133, 2016097]
- Ministry of Science and Technology of the People's Republic of China [MOST2015CB910603]
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
- CAS-TWAS President's Fellowship for International Doctoral Students
- NSFC [91753000]
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Over 150 types of RNA modifications are identified in RNA molecules. Transcriptome profiling is one of the key steps in decoding the epitranscriptomic panorama of these chemical modifications and their potential functions. N-7-methylguanosine (m(7)G) is one of the most abundant modifications present in tRNA, rRNA and mRNA 5'cap, and has critical roles in regulating RNA processing, metabolism and function. Besides its presence at the cap position in mRNAs, m(7)G is also identified in internal mRNA regions. However, its transcriptome-wide distribution and dynamic regulation within internal mRNA regions remain unknown. Here, we have established m7G individual-nucleotide-resolution cross-linking and immunoprecipitation with sequencing (m(7)G miCLIP-seq) to specifically detect internal mRNA m(7)G modification. Using this approach, we revealed that m(7)G is enriched at the 5'UTR region and AG-rich contexts, a feature that is well-conserved across different human/mouse cell lines and mouse tissues. Strikingly, the internal m(7)G modification is dynamically regulated under both H2O2 and heat shock treatments, with remarkable accumulations in the CDS and 3'UTR regions, and functions in promoting mRNA translation efficiency. Consistently, a PCNA 3'UTR minigene reporter harboring the native m(7)G modification site displays both enriched m(7)G modification and increased mRNA translation upon H2O2 treatment compared to the m(7)G site-mutated minigene reporter (G to A). Taken together, our findings unravel the dynamic profiles of internal mRNA m(7)G methylome and highlight m(7)G as a novel epitranscriptomic marker with regulatory roles in translation.
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