title: Competition between a noncoding exon and introns: Gomafu contains tandem UACUAAC repeats and associates with splicing factor-1.
abstract: Gomafu (also referred to as RNCR2/MIAT) was originally identified as a noncoding RNA expressed in a particular set of neurons. Unlike protein-coding mRNAs, the Gomafu RNA escapes nuclear export and stably accumulates in the nucleus, making a unique nuclear compartment. Although recent studies have revealed the functional relevance of Gomafu in a series of physiological processes, the underlying molecular mechanism remains largely uncharacterized. In this report, we identified a chicken homologue of Gomafu using a comparative genomic approach to search for functionally important and conserved sequence motifs among evolutionarily distant species. Unexpectedly, we found that all Gomafu RNA examined shared a distinctive feature: tandem repeats of UACUAAC, a sequence that has been identified as a conserved intron branch point in the yeast Saccharomyces cerevisiae. The tandem UACUAAC Gomafu RNA repeats bind to the SF1 splicing factor with a higher affinity than the divergent branch point sequence in mammals, which affects the kinetics of the splicing reaction in vitro. We propose that the Gomafu RNA regulates splicing efficiency by changing the local concentration of splicing factors within the nucleus.
authors.affiliation: Nakagawa Initiative Research Unit, RIKEN Advanced Science Institute, Hirosawa, Wako, Saitama, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Tsuiji
authors.forename: Rei
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Furuno
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007438:Introns / Q000235:genetics; D007700:Kinetics; D011485:Protein Binding; D034622:RNA Interference; D000072260:RNA Splicing Factors; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020080:Tandem Repeat Sequences; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C517383:Miat long non-coding RNA; D000072260:RNA Splicing Factors; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C107467:SF1 protein, human; D014157:Transcription Factors