Poster abstracts
Poster number 102 submitted by Justin Mabin
Regulation of alternative splicing by U5 small nuclear RNA variants
Justin Mabin (Biomolecular Chemistry, University of Wisconsin Madison), Katherine Senn (Biomolecular Chemistry, University of Wisconsin Madison), Heidi Dvinge (Biomolecular Chemistry, University of Wisconsin Madison)
Abstract:
Alternative splicing (AS) is a highly dynamic and multivariate process that shapes and expands the human transcriptome and proteome. To date, much of the research on AS regulation has focused on splicing co-factors. But, increasing evidence has shown that core-splicing proteins are also involved in regulating AS1. In addition, the spliceosome contains five small nuclear RNAs (snRNAs) that are responsible for carrying out much of the splicing reaction. snRNAs are loaded with their own complement of proteins forming small nuclear ribonucleoprotein (snRNP) complexes that function in spliceosome assembly. Recently, it has been shown that snRNP proteins are differentially expressed across human tissues, hinting at a cell-type specific regulatory role of core snRNP proteins2. However, there is little research aimed at how the core snRNAs may contribute. Here we focus on U5 snRNAs as there have been five U5 snRNA variants previously shown to incorporate into spliceosomes3. Human genome analysis has identified an additional large number of snRNA variant genes. However, their expression remains largely unknown. Our goal was to systematically characterize the expression of the U5 snRNA sequence variants. Preliminary data from our lab suggests that many of these snRNAs are actually expressed in human tissues. We have also identified several novel U5 variants capable of snRNP formation and are currently working to identify which variants are incorporated into spliceosomes. Other preliminary work has shown that perturbations in U5 snRNA variant levels can affect transcript-specific splicing events, suggesting that U5 snRNA variants may have a role in regulating AS. Overall, we hypothesize that U5 snRNA variants are capable of forming variant snRNPs that have a unique subset of splicing co-factors that may target snRNAs to specific splice-sites. Future work will aim to identify variant snRNP compositional differences and their transcriptome-wide AS effects.
References:
1. Papasaikas P, Tejedor JR, Vigevani L and Valcarcel J (2015) Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery. Mol Cell 57, 7–22.
2. Grosso AR, Gomes AQ, Barbosa-Morais NL, Caldeira S, Thorne NP, Grech G, von Lindern M and Carmo-Fonseca M (2008) Tissue-specific splicing factor gene expression signatures. Nucleic Acids Res 36, 4823–4832.
3. Sontheimer EJ and Steitz JA (1992) Three novel functional variants of human U5 small nuclear RNA. Mol Cell Biol 12, 734–746.
Keywords: Alternative splicing, small nuclear RNA, Core spliceosome