SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns

Kazuhiro Fukumura, Rei Yoshimoto, Luca Sperotto, Hyun Seo Kang, Tetsuro Hirose, Kunio Inoue, Michael Sattler, Akila Mayeda

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Human pre-mRNA introns vary in size from under fifty to over a million nucleotides. We searched for essential factors involved in the splicing of human short introns by screening siRNAs against 154 human nuclear proteins. The splicing activity was assayed with a model HNRNPH1 pre-mRNA containing short 56-nucleotide intron. We identify a known alternative splicing regulator SPF45 (RBM17) as a constitutive splicing factor that is required to splice out this 56-nt intron. Whole-transcriptome sequencing of SPF45-deficient cells reveals that SPF45 is essential in the efficient splicing of many short introns. To initiate the spliceosome assembly on a short intron with the truncated poly-pyrimidine tract, the U2AF-homology motif (UHM) of SPF45 competes out that of U2AF65 (U2AF2) for binding to the UHM-ligand motif (ULM) of the U2 snRNP protein SF3b155 (SF3B1). We propose that splicing in a distinct subset of human short introns depends on SPF45 but not U2AF heterodimer.

Original languageEnglish
Article number4910
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 01-12-2021

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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