1. Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.
- Author
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Gosztyla ML, Zhan L, Olson S, Wei X, Naritomi J, Nguyen G, Street L, Goda GA, Cavazos FF, Schmok JC, Jain M, Uddin Syed E, Kwon E, Jin W, Kofman E, Tankka AT, Li A, Gonzalez V, Lécuyer E, Dominguez D, Jovanovic M, Graveley BR, and Yeo GW
- Subjects
- Humans, Gene Expression Regulation, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, RNA metabolism, RNA genetics, Protein Binding, HEK293 Cells, HeLa Cells, Alternative Splicing, Binding Sites, Multiomics, Zinc Fingers, RNA-Binding Proteins metabolism, RNA-Binding Proteins genetics, RNA Splicing
- Abstract
RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation. The examined ZFPs show widespread sequence-specific RNA binding and preferentially bind proximal to transcription start sites. Additionally, several ZFPs associate with their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DNA/RNA-associated protein that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation., Competing Interests: Declaration of interests G.W.Y. is a scientific advisory board (SAB) member of Jumpcode Genomics and a co-founder, member of the board of directors, on the SAB, equity holder, and paid consultant for Eclipse BioInnovations. G.W.Y. is a Distinguished Visiting Professor at the National University of Singapore. G.W.Y.’s interests have been reviewed and approved by UCSD in accordance with its conflict-of-interest policies. B.R.G. is a co-founder and SAB member for RNAConnect., (Copyright © 2024 University of California San Diego. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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