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.
[doi:10.25345/C5TB0Z634]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: ZNF ; RBP ; DBP
Principal Investigators: (in alphabetical order) |
Gene Yeo, UCSD, United States |
Submitting User: | mj2794 |
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1. Gosztyla, M.L., Zhan, L., Olson, S., Wei, X., Naritomi, J., Nguyen, G., Street, L., Goda, G.A., Cavazos, F.F., Schmok, J.C., et al. (2024). Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation. Molecular Cell. https://doi.org/10.1016/j.molcel.2024.08.010.
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