title: Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay.
abstract: Metazoan cells have two pathways for intron removal involving the U2- and U12-type spliceosomes, which contain mostly nonoverlapping sets of small nuclear ribonucleoproteins. We show that in vitro splicing of a U12-type intron assembles an exon junction complex (EJC) that is comparably positioned and contains many of the same components as that deposited by the U2-type spliceosome. The presence of a U12-type intron downstream of a premature termination codon within an open reading frame (ORF) induces nonsense-mediated decay of the mRNA in vivo. These findings suggest a common pathway for EJC assembly by the two spliceosomes and highlight the evolutionary age of the EJC and its downstream functions in gene expression.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
authors.forename: Mei-Di
authors.initials: MD
authors.lastname: Shu
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D018389:Codon, Nonsense; D018076:DNA, Complementary / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007438:Introns; D016297:Mutagenesis, Site-Directed; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000235:genetics* / Q000378:metabolism; D016914:Ribonuclease H / Q000737:chemistry; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D018389:Codon, Nonsense; D018076:DNA, Complementary; D012322:RNA Precursors; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C096986:U12 small nuclear RNA; D012313:RNA; D016914:Ribonuclease H