Emerging insights into the function and structure of the Integrator complex

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.

KEWORDS:

• Integrator
• 3’-end processing
• endonuclease
• transcription attenuation
• RNAPII
• snRNA
• cryo-EM

Acknowledgments

We thank Isaac Fianu and Patrick Cramer for sharing atomic coordinates of the Integrator-PP2A-PEC complex and Alessandro Gardini, Kinga Kamieniarz-Gdula, Tara Best, and Michal Razew for critical comments on the manuscript.

Disclosure statement

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

Additional information

Funding

W.P.G. was supported by the European Research Council (ERC) grant under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 950278)