Integrator subunit 4 is a ‘Symplekin-like’ scaffold that associates with INTS9/11 to form the Integrator cleavage module

Todd R. Albrecht, Sergey P. Shevtsov, Yixuan Wu, Lauren G. Mascibroda, Natoya J. Peart, Kai-Lieh Huang, Iain A. Sawyer, Liang Tong, Miroslav Dundr, Eric Wagner

Research output: Contribution to journalArticle

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Abstract

Integrator (INT) is a transcriptional regulatory complex associated with RNA polymerase II that is required for the 3-end processing of both UsnRNAs and enhancer RNAs. Integrator subunits 9 (INTS9) and INTS11 constitute the catalytic core of INT and are paralogues of the cleavage and polyadenylation specificity factors CPSF100 and CPSF73. While CPSF73/100 are known to associate with a third protein called Symplekin, there is no paralog of Symplekin within INT raising the question of how INTS9/11 associate with the other INT subunits. Here, we have identified that INTS4 is a specific and conserved interaction partner of INTS9/11 that does not interact with either subunit individually. Although INTS4 has no significant homology with Symplekin, it possesses N-terminal HEAT repeats similar to Symplekin but also contains a -sheet rich C-terminal region, both of which are important to bind INTS9/11. We assess three functions of INT including UsnRNA 3-end processing, maintenance of Cajal body structural integrity, and formation of histone locus bodies to conclude that INTS4/9/11 are the most critical of the INT subunits for UsnRNA biogenesis. Altogether, these results indicate that INTS4/9/11 compose a heterotrimeric complex that likely represents the Integrator ‘cleavage module’ responsible for its endonucleolytic activity.

Original languageEnglish (US)
Pages (from-to)4241-4255
Number of pages15
JournalNucleic Acids Research
Volume46
Issue number8
DOIs
StatePublished - Jan 1 2018

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Cleavage And Polyadenylation Specificity Factor
Terminal Repeat Sequences
RNA Polymerase II
Histones
Catalytic Domain
Maintenance
RNA
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Integrator subunit 4 is a ‘Symplekin-like’ scaffold that associates with INTS9/11 to form the Integrator cleavage module. / Albrecht, Todd R.; Shevtsov, Sergey P.; Wu, Yixuan; Mascibroda, Lauren G.; Peart, Natoya J.; Huang, Kai-Lieh; Sawyer, Iain A.; Tong, Liang; Dundr, Miroslav; Wagner, Eric.

In: Nucleic Acids Research, Vol. 46, No. 8, 01.01.2018, p. 4241-4255.

Research output: Contribution to journalArticle

Albrecht, Todd R. ; Shevtsov, Sergey P. ; Wu, Yixuan ; Mascibroda, Lauren G. ; Peart, Natoya J. ; Huang, Kai-Lieh ; Sawyer, Iain A. ; Tong, Liang ; Dundr, Miroslav ; Wagner, Eric. / Integrator subunit 4 is a ‘Symplekin-like’ scaffold that associates with INTS9/11 to form the Integrator cleavage module. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 8. pp. 4241-4255.
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