title: DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes.
abstract: The elongation factors DSIF and NELF are responsible for promoter-proximal RNA polymerase II (Pol II) pausing. NELF is also involved in 3' processing of replication-dependent histone genes, which produce non-polyadenylated mRNAs. Here we show that DSIF and NELF contribute to the synthesis of small nuclear RNAs (snRNAs) through their association with Integrator, the large multisubunit complex responsible for 3' processing of pre-snRNAs. In HeLa cells, Pol II, Integrator, DSIF and NELF accumulate at the 3' end of the U1 snRNA gene. Knockdown of NELF results in misprocessing of U1, U2, U4 and U5 snRNAs, while DSIF is required for proper transcription of these genes. Knocking down NELF also disrupts transcription termination and induces the production of polyadenylated U1 transcripts caused by an enhanced recruitment of cleavage stimulation factor. Our results indicate that NELF plays a key role in determining the post-transcriptional fate of Pol II-transcribed genes.
authors: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors: Junichi
authors: J
authors: Yamamoto
authors: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors: Yuri
authors: Y
authors: Hagiwara
authors: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors: Kunitoshi
authors: K
authors: Chiba
authors: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors: Tomoyasu
authors: T
authors: Isobe
authors: Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
authors: Takashi
authors: T
authors: Narita
authors: Department of Nanoparticle Translational Research, Tokyo Medical University, Tokyo 160-8402, Japan.
authors: Hiroshi
authors: H
authors: Handa
authors: 1] Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan [2] PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
authors: Yuki
authors: Y
authors: Yamaguchi
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C000588765:INTS12 protein, human; C543505:INTS3 protein, human; C581361:INTS4 protein, human; C121427:INTS6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C411985:NSMF protein, human; D009687:Nuclear Proteins; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D025521:Tumor Suppressor Proteins; C405483:U1 small nuclear RNA; C405484:U2 small nuclear RNA; C405482:U4 small nuclear RNA; C405485:U5 small nuclear RNA; D012319:RNA Polymerase II; D004722:Endoribonucleases; C571259:IntS9 protein, human