title: PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion.
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.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Cho
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Heegyum
authors.initials: H
authors.lastname: Moon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Tiing Jen
authors.initials: TJ
authors.lastname: Loh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Oh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Darren Reese
authors.initials: DR
authors.lastname: Williams
authors.affiliation: Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Liao
authors.affiliation: Nantong University, Nantong, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Howard Hughes Medical Institute and Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Xuexiu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: haihongshen@gist.ac.kr.
authors.forename: Haihong
authors.initials: H
authors.lastname: Shen
mesh_terms: D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D000072670:PTB-Associated Splicing Factor; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D000072670:PTB-Associated Splicing Factor; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein; D008156:Luciferases
keywords: Enhancer; Exon 7 splicing; PSF; RNA splicing; Spinal muscular atrophy