| Literature DB >> 31358969 |
Xin Chen1,2, Ang Li3,4, Bao-Fa Sun3,4,5, Ying Yang3,4,5, Ya-Nan Han3,4, Xun Yuan6, Ri-Xin Chen1, Wen-Su Wei1,2, Yanchao Liu6, Chun-Chun Gao3,4, Yu-Sheng Chen3,4, Mengmeng Zhang7, Xiao-Dan Ma1, Zhuo-Wei Liu1,2, Jun-Hang Luo1, Cong Lyu4,8, Hai-Lin Wang4,8, Jinbiao Ma7, Yong-Liang Zhao3,4,5, Fang-Jian Zhou1,2, Ying Huang9, Dan Xie10, Yun-Gui Yang11,12,13.
Abstract
Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C 'reader' recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m5C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.Entities:
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Year: 2019 PMID： 31358969 DOI： 10.1038/s41556-019-0361-y
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824