PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion

Sunghee Cho, Heegyum Moon, Tiing Jen Loh, Hyun Kyung Oh, Darren Reese Williams, D. Joshua Liao, Jianhua Zhou, Michael R. Green, Xuexiu Zheng, Haihong Shen

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease and a leading cause of infant mortality. Deletions or mutations of SMN1 cause SMA, a gene that encodes a SMN protein. SMN is important for the assembly of Sm proteins onto UsnRNA to UsnRNP. SMN has also been suggested to direct axonal transport of β-actin mRNA in neurons. Humans contain a second SMN gene called SMN2 thus SMA patients produce some SMN but not with sufficient levels. The majority of SMN2 mRNA does not include exon 7. Here we show that increased expression of PSF promotes inclusion of exon 7 in the SMN2 whereas reduced expression of PSF promotes exon 7 skipping. In addition, we present evidence showing that PSF interacts with the GAAGGA enhancer in exon 7. We also demonstrate that a mutation in this enhancer abolishes the effects of PSF on exon 7 splicing. Furthermore we show that the RNA target sequences of PSF and tra2β in exon 7 are partially overlapped. These results lead us to conclude that PSF interacts with an enhancer in exon 7 to promote exon 7 splicing of SMN2 pre-mRNA.

Original languageEnglish
Pages (from-to)517-525
Number of pages9
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1839
Issue number6
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

Keywords

  • Enhancer
  • Exon 7 splicing
  • PSF
  • RNA splicing
  • Spinal muscular atrophy

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