Abstract
Spinal muscular atrophy (SMA), the most frequent human congenital motor neuron degenerative disease, is caused by loss-of-function mutations in the highly conserved survival motor neuron gene SMN1. Mutations in SMN could affect several molecular processes, among which aberrant pre-mRNA splicing caused by defective snRNP biogenesis is hypothesized as a major cause of SMA. To date little is known about the interactions of SMN with other splicing factor genes and how SMN affects splicing in vivo. The nematode Caenorhabditis elegans carries a single ortholog of SMN, smn-1, and has been used as a model for studying the molecular functions of SMN. We analyzed RNA splicing of reporter genes in an smn-1 deletion mutant and found that smn-1 is required for efficient splicing at weak 3′ splice sites. Genetic studies indicate that the defective lifespan and motor functions of the smn-1 deletion mutants could be significantly improved by mutations of the splicing factor U2AF large subunit gene uaf-1. In smn-1 mutants we detected a reduced expression of U1 and U5 snRNAs and an increased expression of U2, U4 and U6 snRNAs. Our study verifies an essential role of smn-1 for RNA splicing in vivo, identifies the uaf-1 gene as a potential genetic modifier of smn-1 mutants, and suggests that SMN-1 has multifaceted effects on the expression of spliceosomal snRNAs.
Original language | English (US) |
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Pages (from-to) | 1148-1160 |
Number of pages | 13 |
Journal | RNA biology |
Volume | 11 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2014 |
Keywords
- SMA
- SMN
- Smn-1
- U2AF large subunit
- Uaf-1
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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The survival motor neuron gene smn-1 interacts with the U2AF large subunit gene uaf-1 to regulate Caenorhabditis elegans lifespan and motor functions
Gao, X. (Contributor), Teng, Y. (Contributor), Luo, J. (Contributor), Huang, L. (Contributor), Li, M. (Creator), Zhang, Z. (Contributor), Ma, Y.-C. (Creator) & Ma, L. (Creator), Taylor & Francis, 2015
DOI: 10.6084/m9.figshare.1263573, https://tandf.figshare.com/articles/dataset/The_survival_motor_neuron_gene_i_smn_1_i_interacts_with_the_U2AF_large_subunit_gene_i_uaf_1_i_to_regulate_i_Caenorhabditis_elegans_i_lifespan_and_motor_functions/1263573
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