Integrator complex subunit 12 (INTS12)

Integrator complex subunit 12 (INTS12) is a highly conserved nuclear protein and an essential component of the integrator complex, a multi-subunit assembly that associates with RNA polymerase II to mediate the 3′ end processing of small nuclear RNAs (snRNAs). INTS12 contains a PHD finger domain, which is typical for proteins involved in chromatin-dependent transcriptional regulation, but its key functional domain for integrator activity is a small N-terminal microdomain responsible for protein-protein interactions and stabilization of other integrator subunits. In addition to its canonical role in snRNA maturation, INTS12 binds throughout the genome at transcriptionally active sites and regulates expression of genes involved in protein synthesis, cell translation, and chromatin architecture. Recent studies implicate INTS12 in the maintenance of HIV latency, as knockdown of INTS12 in HIV-infected cells leads to activation of viral transcription and enhances the effect of latency-reversing agents, without causing overt cell toxicity. Genetic variations in the INTS12 gene locus have been associated with alterations in lung function and the risk for chronic obstructive pulmonary disease (COPD). Overall, INTS12 functions as both a transcriptional regulator and a core processing factor for RNA maturation, with emerging significance in human disease mechanisms including HIV infection and pulmonary function.

Other names

INTS12Integrator complex subunit 12PHF22PHD finger protein 22SBBI22Int12INT12Hypothetical nuclear factor SBBI22

Synergistic latency reactivation by removal of transcriptional silencing in HIV; Enhancement of HIV transcription by combinatorial knockdown with latency-reversing agents; Null (no classic agonist, antagonist, inhibitor mechanism described)