Paper

Integrator Subunit 4 is a 'Symplekin-like' Scaffold that Associates with INTS9/11 to Form the Integrator Cleavage Module

Albrecht, Todd R, Peart, Natoya J, Wagner, Eric J, Mascibroda, Lauren G, Shevtsov, Sergey P, Dundr, Miroslav, Sawyer, Iain A

2017

Overview

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 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.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: DNA-directed RNA polymerase / Homology / Molecular Biology / Polyadenylation / RNA polymerase / Transcription