Methylation of PP2A controls RNAPII processivity and transcriptional integrity [ChIP-Seq]

ABSTRACT: In higher eukaryotes, PP2A phosphatase activity is embedded within two fundamentally different complex types. Canonical PP2A complexes are usually a trimeric assembly of scaffold, catalytic and regulatory subunits. Noncanonical PP2A, instead, is a dimeric component of the Integrator complex and, as we show here, the most prevalent nuclear form of the phosphatase. The majority of cellular PP2A is subjected to carboxyl-terminal methylation of its catalytic core (PP2CA) by the LCMT1 methyltransferase, but the global function of methyl-PP2CA remains controversial, and its role within Integrator is not explored. Here we show that while LCMT1 is dispensable for the assembly of most PP2A complexes, the PP2CA methylation cycle modulates Integrator’s phosphatase activity at chromatin. In fact, actively transcribing RNAPII can recruit the PPME1 phosphodiesterase to quench dephosphorylation of the CTD and boost elongation. Our data suggests that Integrator-PP2A works as a global rheostat for RNAPII processivity, ensuring the fidelity of co-transcriptional processing to ultimately preserve transcriptional integrity

ORGANISM(S): Homo sapiens

PROVIDER: GSE306185 | GEO | 2026/10/05

REPOSITORIES: GEO