Dataset Information

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

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 array-based 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 oncogenic mutant, 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.

SUBMITTER: Liu L

PROVIDER: S-EPMC6412114 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Liu Lichao L Li Tong T Song Guang G He Qingxia Q Yin Yafei Y Lu J Yuyang JY Bi Xianju X Wang Kaili K Luo Sai S Chen Yu-Sheng YS Yang Ying Y Sun Bao-Fa BF Yang Yun-Gui YG Wu Jiawei J Zhu Heng H Shen Xiaohua X

Nucleic acids research 20190301 5

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 array-based 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 en ...[more]

PMID: 30698743

Similar Datasets

Project description:This study presents an analysis of the small molecule bioactivity profiles across large quantities of diverse protein families represented in PubChem BioAssay. We compared the bioactivity profiles of FDA approved drugs to non-FDA approved compounds, and report several distinct patterns characteristic of the approved drugs. We found that a large fraction of the previously reported higher target promiscuity among FDA approved compounds, compared to non-FDA approved bioactives, was frequently due to cross-reactivity within rather than across protein families. We identified 804 potentially novel protein target candidates for FDA approved drugs, as well as 901 potentially novel target candidates with active non-FDA approved compounds, but no FDA approved drugs with activity against these targets. We also identified 486348 potentially novel compounds active against the same targets as FDA approved drugs, as well as 153402 potentially novel compounds active against targets without active FDA approved drugs. By quantifying the agreement among replicated screens, we estimated that more than half of these novel outcomes are reproducible. Using biclustering, we identified many dense clusters of FDA approved drugs with enriched activity against a common set of protein targets. We also report the distribution of compound promiscuity using a Bayesian statistical model, and report the sensitivity and specificity of two common methods for identifying promiscuous compounds. Aggregator assays exhibited greater accuracy in identifying highly promiscuous compounds, while PAINS substructures were able to identify a much larger set of "middle range" promiscuous compounds. Additionally, we report a large number of promiscuous compounds not identified as aggregators or PAINS. In summary, the results of this study represent a rich reference for selecting novel drug and target protein candidates, as well as for eliminating candidate compounds with unselective activities.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets