Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• The Integrator complex is a metazoan-specific assembly with 14 subunits.
• It possesses endonuclease activity crucial for cleaving nascent RNA transcripts.

Purpose of the Study:

• To identify and characterize a novel complex involving the Integrator and protein phosphatase 2A core enzyme (PP2A-AC).
• To elucidate the structure and function of this newly identified complex, termed INTAC.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine the 3.5-angstrom-resolution structure of the INTAC complex.
• Biochemical assays to assess the enzymatic activities of INTAC.

Main Results:

• The structure reveals a cruciform-shaped scaffold formed by Integrator subunits and PP2A-AC.
• INTAC functions as a noncanonical PP2A holoenzyme, dephosphorylating RNA polymerase II at specific serine residues (Ser2, Ser5, Ser7).
• The complex integrates both RNA cleavage and RNA polymerase II dephosphorylation activities.

Conclusions:

• The study identifies and structurally characterizes the INTAC complex, integrating Integrator and PP2A-AC.
• INTAC plays a regulatory role in transcription through dual enzymatic activities.
• This work expands the known functions of PP2A to transcriptional regulation.