A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation initiation

Abstract

A significant number of viral and cellular mRNAs utilize cap‐independent translation, employing mechanisms distinct from those of canonical translation initiation. Cap‐independent translation requires noncanonical, cellular RNA‐binding proteins; however, the roles of such proteins in ribosome recruitment and translation initiation are not fully understood. This work demonstrates that a nucleo‐cytoplasmic SR protein, SRp20, functions in internal ribosome entry site (IRES)‐mediated translation of a viral RNA. We found that SRp20 interacts with the cellular RNA‐binding protein, PCBP2, a protein that binds to IRES sequences within the genomic RNAs of certain picornaviruses and is required for viral translation. We utilized in vitro translation in HeLa cell extracts depleted of SRp20 to demonstrate that SRp20 is required for poliovirus translation initiation. Targeting SRp20 in HeLa cells with short interfering RNAs resulted in inhibition of SRp20 protein expression and a corresponding decrease in poliovirus translation. Our data have identified a previously unknown function of an SR protein (i.e., the stimulation of IRES‐mediated translation), further documenting the multifunctional nature of this important class of cellular RNA‐binding proteins.