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

Autor:	Dasilva LF; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Blumenthal E; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA.; Medical Scientist Training Program and Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA., Beckedorff F; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Cingaram PR; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Gomes Dos Santos H; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Edupuganti RR; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Zhang A; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Dokaneheifard S; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Aoi Y; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Yue J; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Kirstein N; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Tayari MM; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA., Shilatifard A; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Shiekhattar R; Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10th Avenue, Miami, FL 33136, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Nov 05; Vol. 7 (45), pp. eabe3393. Date of Electronic Publication: 2021 Nov 03.
DOI:	10.1126/sciadv.abe3393
Abstrakt:	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.
Databáze:	MEDLINE
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