Skip to main content
Article
TIA1 Prevents Skipping of a Critical Exon Associated with Spinal Muscular Atrophy
Molecular and Cellular Biology
  • Natalia N. Singh, Iowa State University
  • Joonbae Seo, Iowa State University
  • Eric W. Ottesen, Iowa State University
  • Maria Shishimorova, Iowa State University
  • Dhruva Bhattacharya, Iowa State University
  • Ravindra N. Singh, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
1-1-2011
DOI
10.1128/MCB.00945-10
Abstract
Prevention of skipping of exon 7 during pre-mRNA splicing of Survival Motor Neuron 2 (SMN2) holds the promise for cure of spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. Here, we report T-cell-restricted intracellular antigen 1 (TIA1) and TIA1-related (TIAR) proteins as intron-associated positive regulators of SMN2 exon 7 splicing. We show that TIA1/TIAR stimulate exon recognition in an entirely novel context in which intronic U-rich motifs are separated from the 5′ splice site by overlapping inhibitory elements. TIA1 and TIAR are modular proteins with three N-terminal RNA recognition motifs (RRMs) and a C-terminal glutamine-rich (Q-rich) domain. Our results reveal that any one RRM in combination with a Q domain is necessary and sufficient for TIA1-associated regulation of SMN2 exon 7 splicing in vivo. We also show that increased expression of TIA1 counteracts the inhibitory effect of polypyrimidine tract binding protein, a ubiquitously expressed factor recently implicated in regulation of SMN exon 7 splicing. Our findings expand the scope of TIA1/TIAR in genome-wide regulation of alternative splicing under normal and pathological conditions
Comments

This is an article from Molecular and Cellular Biology 31 (2011): 935, doi:10.1128/MCB.00945-10. Posted with permission.

Copyright Owner
American Society for Microbiology
Language
en
File Format
application/pdf
Citation Information
Natalia N. Singh, Joonbae Seo, Eric W. Ottesen, Maria Shishimorova, et al.. "TIA1 Prevents Skipping of a Critical Exon Associated with Spinal Muscular Atrophy" Molecular and Cellular Biology Vol. 31 Iss. 5 (2011) p. 935 - 954
Available at: http://works.bepress.com/eric-ottesen/3/