RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex

Abstract

Lay Summary: The Human Silencing Hub (HUSH) complex provides a genome-wide immunosurveillance system which protects our genome from invading foreign retroelements, such as HIV-like viruses. HUSH is an epigenetic repressor complex that must distinguish these foreign invaders from our own host genes, and immediately silence the invaders. This silencing by HUSH is dependent on RNA transcription, implying at least one of the three core HUSH components binds RNA. Here we identify Periphilin as the major RNA-binding protein of the HUSH complex. We show that RNA-binding by Periphilin is essential for HUSH activity and that artificially recruiting Periphilin to an RNA transcript silences that transcript.