Insight into novel RNA-binding activities via large-scale analysis of lncRNA-bound proteome and IDH1-bound transcriptome

Lichao Liu, Tong Li, Guang Song, Qingxia He, Yafei Yin, J. Yuyang Lu, Xianju Bi, Kaili Wang, Sai Luo, Yu Sheng Chen, Ying Yang, Bao Fa Sun, Yun Gui Yang, Jiawei Wu, Heng Zhu, Xiaohua Shen

Research output: Contribution to journalArticlepeer-review

Abstract

RNA-binding proteins (RBPs) play pivotal roles in directing RNA fate and function. Yet the current annotation of RBPs is largely limited to proteins carrying known RNA-binding domains. To systematically reveal dynamic RNA-protein interactions, we surveyed the human proteome by a protein arraybased approach and identified 671 proteins with RNA-binding activity. Among these proteins, 525 lack annotated RNA-binding domains and are enriched in transcriptional and epigenetic regulators, metabolic enzymes, and small GTPases. Using an improved CLIP (crosslinking and immunoprecipitation) method, we performed genome-wide target profiling of isocitrate dehydrogenase 1 (IDH1), a novel RBP. IDH1 binds to thousands of RNA transcripts with enriched functions in transcription and chromatin regulation, cell cycle and RNA processing. Purified IDH1, but not an oncogenicmutant, binds directly to GA- or AU-rich RNA that are also enriched in IDH1 CLIP targets. Our study provides useful resources of unconventional RBPs and IDH1-bound transcriptome, and convincingly illustrates, for the first time, the in vivo and in vitro RNA targets and binding preferences of IDH1, revealing an unanticipated complexity of RNA regulation in diverse cellular processes.

Original languageEnglish (US)
Pages (from-to)2244-2262
Number of pages19
JournalNucleic acids research
Volume47
Issue number5
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Genetics

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