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Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts

Open access
Sanford, Jeremy R., Wang, Xin, Mort, Matthew, VanDuyn, Natalia, Cooper, David N., Mooney, Sean D., Edenberg, Howard J., Liu, Yunlong·2009·Genome Research

Abstract

Metazoan genes are encrypted with at least two superimposed codes: the genetic code to specify the primary structure of proteins and the splicing code to expand their proteomic output via alternative splicing. Here, we define the specificity of a central regulator of pre-mRNA splicing, the conserved, essential splicing factor SFRS1. Cross-linking immunoprecipitation and high-throughput sequencing (CLIP-seq) identified 23,632 binding sites for SFRS1 in the transcriptome of cultured human embryonic kidney cells. SFRS1 was found to engage many different classes of functionally distinct transcripts including mRNA, miRNA, snoRNAs, ncRNAs, and conserved intergenic transcripts of unknown function. The majority of these diverse transcripts share a purine-rich consensus motif corresponding to the canonical SFRS1 binding site. The consensus site was not only enriched in exons cross-linked to SFRS1 in vivo, but was also enriched in close proximity to splice sites. mRNAs encoding RNA processing factors were significantly overrepresented, suggesting that SFRS1 may broadly influence the post-transcriptional control of gene expression in vivo. Finally, a search for the SFRS1 consensus motif within the Human Gene Mutation Database identified 181 mutations in 82 different genes that disrupt predicted SFRS1 binding sites. This comprehensive analysis substantially expands the known roles of human SR proteins in the regulation of a diverse array of RNA transcripts.

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Metadata

Authors
Sanford, J. R., Wang, X., Mort, M., VanDuyn, N., Cooper, D. N., Mooney, S. D., Edenberg, H. J., & Liu, Y.
Venue
Genome Research
Published
2008-12-30
Volume
19
Issue
3
Pages
381-394
ISSN
1088-9051 (ISSN-L)
OpenAlex
W2106309105
Cited by
313
References
79
Type
posted content
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. https://app.cochat.ai/papers/10.1101/gr.082503.108
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Sanford, J. R., Wang, X., Mort, M., VanDuyn, N., Cooper, D. N., Mooney, S. D., Edenberg, H. J., & Liu, Y. (2009). Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Research. https://doi.org/10.1101/gr.082503.108

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