Regulation of the Integrator complex by SUMO conjugation

BRAGADO, LAUREANO; MAGALNIK, MELINA; SREBROW, ANABELLA

Congreso; Congreso conjunto SAIB-SAMIGE 2021; 2021

The set of proteins required for the proper expression and metabolism of snRNAs includes the Integrator complex, which is responsible for the 3?-end processing of snRNAs (1). The subunits INTS4, INTS9 and INTS11 compose the catalytic core of the Integrator complex. Interestingly, this 3?-cleavage is affected upon overexpression of USPL1, a SUMO isopeptidase (2), suggesting that the maintenance of SUMOylation levels is critical for adequate snRNA 3?-end processing. Particularly, the SUMOylation of INTS11 can be downregulated by USPL1 (3). Through site-specific mutagenesis we had generated an INTS11 3KR mutant, whose SUMOylation is drastically reduced (4). When silencing endogenous INTS11 (5), this 3KR mutant is unable to achieve the 3?-end processing of precursor snRNAs (6) compared to the wild-type and a catalytic inactive version of INTS11 (E203Q), which can be SUMOylated (4). INTS11 3KR preserves its interaction with the catalytic core (7-top), but it seems that INTS11 SUMOylation is important to assemble the whole Integrator complex (7-bottom). Moreover, this INTS11 SUMO mutant showed a more cytoplasmatic localization compared with the wild-type protein (8).