Integrator enforces the fidelity of transcriptional termination at protein-coding genes

Integrator regulates the 3′-end processing and termination of multiple classes of noncoding RNAs. Depletion of INTS11, the catalytic subunit of Integrator, or ectopic expression of its catalytic dead enzyme impairs the 3′-end processing and termination of a set of protein-coding transcripts termed I...

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Bibliographic Details
Published in:Science advances 2021-11, Vol.7 (45), p.eabe3393-eabe3393
Main Authors: Dasilva, Lucas Ferreira, Blumenthal, Ezra, Beckedorff, Felipe, Cingaram, Pradeep Reddy, Gomes Dos Santos, Helena, Edupuganti, Raghu Ram, Zhang, Anda, Dokaneheifard, Sadat, Aoi, Yuki, Yue, Jingyin, Kirstein, Nina, Tayari, Mina Masoumeh, Shilatifard, Ali, Shiekhattar, Ramin
Format: Article
Language:English
Subjects:
Biochemistry
Biomedicine and Life Sciences
Genetics
Molecular Biology
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Summary:Integrator regulates the 3′-end processing and termination of multiple classes of noncoding RNAs. Depletion of INTS11, the catalytic subunit of Integrator, or ectopic expression of its catalytic dead enzyme impairs the 3′-end processing and termination of a set of protein-coding transcripts termed Integrator-regulated termination (IRT) genes. This defect is manifested by increased RNA polymerase II (RNAPII) readthrough and occupancy of serine-2 phosphorylated RNAPII, de novo trimethylation of lysine-36 on histone H3, and a compensatory elevation of the cleavage and polyadenylation (CPA) complex beyond the canonical polyadenylation sites. 3′ RNA sequencing reveals that proximal polyadenylation site usage relies on the endonuclease activity of INTS11. The DNA sequence encompassing the transcription end sites of IRT genes features downstream polyadenylation motifs and an enrichment of GC content that permits the formation of secondary structures within the 3′UTR. Together, this study identifies a subset of protein-coding transcripts whose 3′ end processing requires the Integrator complex.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abe3393