DSIF and NELF interact with Integrator to specify the correct post-transcriptional fate of snRNA genes

• Published in: Nature communications 2014-06, Vol.5 (1), p.4263-4263, Article 4263
• Main Authors: Yamamoto, Junichi, Hagiwara, Yuri, Chiba, Kunitoshi, Isobe, Tomoyasu, Narita, Takashi, Handa, Hiroshi, Yamaguchi, Yuki
• Format: Article
• Language: English
• Subjects: 38; 38/15; 38/89; 631/337/384/521; 631/337/572; 631/45/612/822; Carrier Proteins - metabolism; DNA-Binding Proteins - metabolism; Endoribonucleases - metabolism; Gene Knockdown Techniques; HeLa Cells; Humanities and Social Sciences; Humans; Intracellular Signaling Peptides and Proteins; multidisciplinary; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Ribosomal Proteins - metabolism; RNA Polymerase II - metabolism; RNA, Small Nuclear - metabolism; RNA-Binding Proteins; Science; Science (multidisciplinary); Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Elongation Factors - genetics; Transcriptional Elongation Factors - metabolism; Tumor Suppressor Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5263

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. The elongation factors DSIF and NELF have established roles in polymerase pausing, elongation and 3'-end processing of replication-dependent histone mRNAs. Here the authors demonstrate that DSIF and NELF form a complex with Integrator and allow proper 3'-processing of snRNA transcripts by preventing the recruitment of CstF.