Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts

Jeremy R. Sanford, Xin Wang, Matthew Mort, Natalia Vanduyn, David N. Cooper, Sean D. Mooney, Howard Edenberg, Yunlong Liu

Research output: Contribution to journalArticle

200 Citations (Scopus)

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 SFRSI binding sites. This comprehensive analysis substantially expands the known roles of human SR proteins in the regulation of a diverse array of RNA transcripts.

Original languageEnglish
Pages (from-to)381-394
Number of pages14
JournalGenome Research
Volume19
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Binding Sites
RNA
Small Nucleolar RNA
Protein Splicing
Genes
Genetic Code
Messenger RNA
Mutation
RNA Precursors
Alternative Splicing
MicroRNAs
Transcriptome
Immunoprecipitation
Proteomics
Exons
Databases
Kidney
Gene Expression
RNA Splicing Factors
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Sanford, J. R., Wang, X., Mort, M., Vanduyn, N., Cooper, D. N., Mooney, S. D., ... Liu, Y. (2009). Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Research, 19(3), 381-394. https://doi.org/10.1101/gr.082503.108

Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. / Sanford, Jeremy R.; Wang, Xin; Mort, Matthew; Vanduyn, Natalia; Cooper, David N.; Mooney, Sean D.; Edenberg, Howard; Liu, Yunlong.

In: Genome Research, Vol. 19, No. 3, 03.2009, p. 381-394.

Research output: Contribution to journalArticle

Sanford, JR, Wang, X, Mort, M, Vanduyn, N, Cooper, DN, Mooney, SD, Edenberg, H & Liu, Y 2009, 'Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts', Genome Research, vol. 19, no. 3, pp. 381-394. https://doi.org/10.1101/gr.082503.108
Sanford JR, Wang X, Mort M, Vanduyn N, Cooper DN, Mooney SD et al. Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Research. 2009 Mar;19(3):381-394. https://doi.org/10.1101/gr.082503.108
Sanford, Jeremy R. ; Wang, Xin ; Mort, Matthew ; Vanduyn, Natalia ; Cooper, David N. ; Mooney, Sean D. ; Edenberg, Howard ; Liu, Yunlong. / Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. In: Genome Research. 2009 ; Vol. 19, No. 3. pp. 381-394.
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