Picornavirus Modification of a Host mRNA Decay Protein

Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, USA.
mBio (Impact Factor: 6.79). 10/2012; 3(6). DOI: 10.1128/mBio.00431-12
Source: PubMed


Due to the limited coding capacity of picornavirus genomic RNAs, host RNA binding proteins play essential roles during viral translation and RNA replication. Here we describe experiments suggesting that AUF1, a host RNA binding protein involved in mRNA decay, plays a role in the infectious cycle of picornaviruses such as poliovirus and human rhinovirus. We observed cleavage of AUF1 during poliovirus or human rhinovirus infection, as well as interaction of this protein with the 5' noncoding regions of these viral genomes. Additionally, the picornavirus proteinase 3CD, encoded by poliovirus or human rhinovirus genomic RNAs, was shown to cleave all four isoforms of recombinant AUF1 at a specific N-terminal site in vitro. Finally, endogenous AUF1 was found to relocalize from the nucleus to the cytoplasm in poliovirus-infected HeLa cells to sites adjacent to (but distinct from) putative viral RNA replication complexes.

This study derives its significance from reporting how picornaviruses like poliovirus and human rhinovirus proteolytically cleave a key player (AUF1) in host mRNA decay pathways during viral infection. Beyond cleavage of AUF1 by the major viral proteinase encoded in picornavirus genomes, infection by poliovirus results in the relocalization of this host cell RNA binding protein from the nucleus to the cytoplasm. The alteration of both the physical state of AUF1 and its cellular location illuminates how small RNA viruses manipulate the activities of host cell RNA binding proteins to ensure a faithful intracellular replication cycle.

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    • "The proteins hnRNP K and hnRNP A1 interact with the 5′ UTR of EV-A71, and are important for viral RNA replication and virion production [53]. Poliovirus RNA also interacts with hnRNP C [54] [55], while hnRNP D was also cleaved by polioviral 3CD protein [56]. The differential regulation of hnRNP H3 could affect the pathogenesis and replication efficiency of the viruses. "
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    • "This is noticed at the level of transcription, mRNA processing, nucleocytoplasmic transport, translation, or RNA granules composition. Among other proteins, proteolysis affects splicing factors, RNAprocessing proteins, RNA helicases, nuclear pore factors, stress granules assembly factors or antiviral response proteins (Almstead and Sarnow, 2007; Barral et al., 2009; Castello et al., 2009; Chase et al., 2014; Chase and Semler, 2014; Chen et al., 2013; Lawrence et al., 2012; Mukherjee et al., 2011; Park et al., 2010; Pineiro et al., 2012; Rozovics et al., 2012; Shiroki et al., 1999; Watters and Palmenberg, 2011; Weng et al., 2009; White et al., 2007). Particularly well documented is the modification of the host translation machinery, which is subverted to favor viral RNA translation and replication. "
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