期刊
NUCLEIC ACIDS RESEARCH
卷 47, 期 5, 页码 2533-2545出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky1250
关键词
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资金
- National Natural Science Foundation of China [81673454, 81672608, 81472470, 31801197, 81572270]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2014A030306025]
- Guangdong Provincial Key Laboratory of Construction Foundation [2017B030314030]
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation [2017B030314026]
- Fundamental Research Funds for the Central Universities (Sun Yat-sen University) [16ykpy09]
- China Postdoctoral Science Foundation [2018M643354]
Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m(1)A) and 3-methylcytidine (m(3)C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m(1)A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs) around the anticodon regions. tDRs are conserved among species, which strengthen the ribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Our discovery opens a potential and novel paradigm of tRNA demethylase, which regulates biological functions via generation of tDRs.
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