title: Skipping of an alternative intron in the srsf1 3' untranslated region increases transcript stability.
abstract: The srsf1 gene encodes serine/arginine-rich splicing factor 1 (SRSF1) that participates in both constitutive and alternative splicing reactions. This gene possesses two ultraconserved elements in the 3' untranslated region (UTR). Skipping of an alternative intron between the two elements has no effect on the protein-coding sequence, but it generates a premature stop codon (PTC)-containing mRNA isoform, whose degradation is considered to depend on nonsense-mediated mRNA decay (NMD). However, several cell lines (HCT116, RKO, HeLa, and WI38 cells) constitutively expressed significant amounts of the srsf1 PTC variant. HCT116 cells expressed the PTC variant nearly equivalent to the major isoform that includes the alternative intron in the 3' UTR. Inhibition of NMD by silencing a key effecter UPF1 or by treatment with cycloheximide failed to increase amounts of the PTC variant in HCT116 cells, and the PTC variant was rather more stable than the major isoform in the presence of actinomycin D. Our results suggest that the original stop codon may escape from the NMD surveillance even in skipping of the alternative intron. The srsf1 gene may produce an alternative splice variant having truncated 3' UTR to relief the microRNA- and/or RNA-binding protein-mediated control of translation or degradation.
authors.affiliation: Department of Stress Science, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Akaike
authors.forename: Ken
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kajita
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kuwano
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.forename: Kensei
authors.initials: K
authors.lastname: Nishida
authors.forename: Seung Wan
authors.initials: SW
authors.lastname: Kang
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D001483:Base Sequence; D045325:HCT116 Cells; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D059368:RNA Isoforms; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors
chemical_list: D020413:3' Untranslated Regions; D009687:Nuclear Proteins; D059368:RNA Isoforms; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors