RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific Journal Article
| Authors: | Ray, D.; Laverty, K. U.; Jolma, A.; Nie, K.; Samson, R.; Pour, S. E.; Tam, C. L.; von Krosigk, N.; Nabeel-Shah, S.; Albu, M.; Zheng, H.; Perron, G.; Lee, H.; Najafabadi, H.; Blencowe, B.; Greenblatt, J.; Morris, Q.; Hughes, T. R. |
| Article Title: | RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific |
| Abstract: | Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)—proteins that associate with RNA but lack known RNA-binding domains (RBDs). The vast majority of ucRBPs have uncharacterized RNA-binding specificities. We analyzed 492 human ucRBPs for intrinsic RNA-binding in vitro and identified 23 that bind specific RNA sequences. Most (17/23), including 8 ribosomal proteins, were previously associated with RNA-related function. We identified the RBDs responsible for sequence-specific RNA-binding for several of these 23 ucRBPs and surveyed whether corresponding domains from homologous proteins also display RNA sequence specificity. CCHC-zf domains from seven human proteins recognized specific RNA motifs, indicating that this is a major class of RBD. For Nudix, HABP4, TPR, RanBP2-zf, and L7Ae domains, however, only isolated members or closely related homologs yielded motifs, consistent with RNA-binding as a derived function. The lack of sequence specificity for most ucRBPs is striking, and we suggest that many may function analogously to chromatin factors, which often crosslink efficiently to cellular DNA, presumably via indirect recruitment. Finally, we show that ucRBPs tend to be highly abundant proteins and suggest their identification in RNA interactome capture studies could also result from weak nonspecific interactions with RNA. © 2023, The Author(s). |
| Keywords: | genetics; metabolism; protein binding; rna binding protein; rna; rna-binding proteins; messenger rna; rna, messenger; ribosomal proteins; ribosome protein; myogenic factor; myogenic regulatory factors; humans; human; rna-binding domain; habp4 protein, human; rna-binding motifs |
| Journal Title: | Scientific Reports |
| Volume: | 13 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-03-31 |
| Start Page: | 5238 |
| Language: | English |
| DOI: | 10.1038/s41598-023-32245-9 |
| PUBMED: | 37002329 |
| PROVIDER: | scopus |
| PMCID: | PMC10066285 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Quaid Morris -- Export Date: 1 May 2023 -- Source: Scopus |
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