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Review
. 2021 Oct;12(5):251-265.
doi: 10.1080/21541264.2022.2047583. Epub 2022 Mar 20.

Emerging insights into the function and structure of the Integrator complex

Affiliations
Review

Emerging insights into the function and structure of the Integrator complex

Moritz M Pfleiderer et al. Transcription. 2021 Oct.

Abstract

The Integrator was originally discovered as a specialized 3'-end processing endonuclease complex required for maturation of RNA polymerase II (RNAPII)-dependent small nuclear RNAs (snRNAs). Since its discovery, Integrator's spectrum of substrates was significantly expanded to include non-polyadenylated long noncoding RNAs (lncRNA), enhancer RNAs (eRNAs), telomerase RNA (tertRNA), several Herpesvirus transcripts, and messenger RNAs (mRNAs). Recently emerging transcriptome-wide studies reveled an important role of the Integrator in protein-coding genes, where it contributes to gene expression regulation through promoter-proximal transcription attenuation. These new functional data are complemented by several structures of Integrator modules and higher-order complexes, providing mechanistic insights into Integrator-mediated processing events. In this work, we summarize recent progress in our understanding of the structure and function of the Integrator complex.

Keywords: 3’-end processing; Integrator; RNAPII; cryo-EM; endonuclease; snRNA; transcription attenuation.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Different modes of Integrator function.
Figure 2.
Figure 2.
Structure of the integrator-PP2A complex.
Figure 3.
Figure 3.
Integrator association with RNAPII and activation of the endonuclease.

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References

    1. Baillat D, Hakimi M-A, Näär AM, et al. Integrator, a Multiprotein Mediator of Small Nuclear RNA Processing, Associates with the C-Terminal Repeat of RNA Polymerase II. Cell. 2005;123(2):265–276. - PubMed
    1. Lai F, Gardini A, Zhang A, et al. Integrator mediates the biogenesis of enhancer RNAs. Nature. 2015;525(7569):399–403. - PMC - PubMed
    1. Cazalla D, Xie M, Steitz JA.. A Primate Herpesvirus Uses the Integrator Complex to Generate Viral MicroRNAs. Mol Cell. 2011;43(6):982–992. - PMC - PubMed
    1. Rubtsova MP, Vasilkova DP, Moshareva MA, et al. Integrator is a key component of human telomerase RNA biogenesis. Sci Rep. 2019;9(1). DOI:10.1038/s41598-018-38297-6. - DOI - PMC - PubMed
    1. Xie M, Zhang W, Shu M-D, et al. The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends. Genes Dev. 2015;29(14):1552–1564. - PMC - PubMed

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