Multivalent Interactions Between the Picornavirus 3C(D) Main Protease and RNA Oligonucleotides Induce Liquid-Liquid Phase Separation.

ABSTRACT: The picornavirus 3CD protein is a precursor to the 3C main protease and the 3D RNA-dependent RNA polymerase. In addition to its functions in proteolytic processing of the virus polyprotein and cleavage of key host factors, the 3C domain interacts with cis-acting replication elements (CREs) within the viral genome to regulate replication and translation events. We investigated the molecular determinants of RNA binding to 3C using a wide range of biophysical and computational methods. These studies showed that 3C binds to a broad spectrum of RNA oligonucleotides, displaying minimal sequence and structure dependence, at least for these shorter RNAs. However, they also uncovered a novel aspect of these interactions, that is, 3C-RNA binding can induce liquid-liquid phase separation (LLPS), with

SUBMITTER: Mondal S 

PROVIDER: S-EPMC12656920 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature