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

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Publication Date


Document Type



Biochemistry | Genetics and Genomics | Molecular Biology | Nervous System Diseases


Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease and a leading cause of infant mortality. Deletions or mutations in SMN1, a gene that encodes an SMN protein, which regulates assembly/disassembly of U snRNP and is suggested to direct axonal transport of beta-actin mRNA in neurons, are responsible for most cases of SMA disease. However, humans contain a second SMN gene called SMN2. Unlike SMN1, the majority of SMN2 mRNA don't include exon 7. Here we show that increased expression of PSF significantly promotes inclusion of exon 7 in the SMN2 and SMN1 mRNA, whereas reduced expression of PSF promotes exon 7 skipping in various cell lines and in fibroblast cells from SMA patients. 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 tra2beta 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.


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

DOI of Published Version



Cho S, Moon H, Loh TJ, Oh HK, Williams DR, Liao DJ, Zhou J, Green MR, Zheng X, Shen H. PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion. Biochim Biophys Acta. 2014 Mar 14. doi: 10.1016/j.bbagrm.2014.03.003. Link to article on publisher's site

Journal/Book/Conference Title

Biochimica et biophysica acta

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Link to Article in PubMed

PubMed ID