Distinct roles of the R3H and RRM domains in poly(A)-specific ribonuclease structural integrity and catalysis

► We investigate the roles of three RNA-binding domains in PARN structure/function. ► The R3H domain can bind with various oligonucleotides with no preference. ► Removal of the R3H domain dissociates PARN into active monomers. ► Three RNA-binding sites act cooperatively in binding with long poly(A) substrates.