Metazoan gene promoters typically support bidirectional transcription, both of stable pre-mRNAs and of divergent, unstable antisense RNAs known as promoter upstream transcripts (PROMPTs). The mechanism of this bidirectional difference in expression is unclear; one possibility is that the enrichment of binding sites of U1 small nuclear ribonucleoproteins (U1 snRNPs) in pre-mRNAs compared with PROMPTs protects the nascent pre-mRNAs from endonucleases. The Integrator complex has RNA endonuclease activity that has a role in transcription termination of some non-coding RNAs and non-productive pre-mRNAs. Yang, Li et al. now report that PROMPT cleavage by Integrator is important for the preferential transcription of pre-mRNA.

Integrator is tightly associated with RNA polymerase II (Pol II), including with its regulatory C-terminal domain, phosphorylation of which is important for transcription regulation. Depletion of Integrator and ChIP–seq analyses of the genomic distribution of differentially phosphorylated Pol II complexes indicated that Integrator supports the distribution of the different Pol II complexes at active promoters and genes, in a manner that favours pre-mRNA transcription.