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 3a'2 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. © 2014 Macmillan Publishers Limited. All rights reserved.