title: Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.
abstract: The C-terminal domain (CTD) of RNA polymerase II (RNAPII) is an essential component of transcriptional regulation and RNA processing of protein-coding genes. A large body of data also implicates the CTD in the transcription and processing of RNAPII-mediated small nuclear RNAs (snRNAs). However, the identity of the complex (or complexes) that associates with the CTD and mediates the processing of snRNAs has remained elusive. Here, we describe an RNA polymerase II complex that contains at least 12 novel subunits, termed the Integrator, in addition to core RNAPII subunits. Two of the Integrator subunits display similarities to the subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. We show that Integrator is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans and directly interacts with the C-terminal domain of the RNA polymerase II largest subunit.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baillat
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
authors.forename: Anders M
authors.initials: AM
authors.lastname: Näär
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
authors.forename: Neil
authors.initials: N
authors.lastname: Cooch
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D004722:Endoribonucleases; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D012313:RNA / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012342:RNA, Small Nuclear; D011993:Recombinant Fusion Proteins; D012313:RNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012319:RNA Polymerase II; D004722:Endoribonucleases; C505818:INTS11 protein, human