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A single host-cell protein, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNP C1/C2), has been demonstrated to promote the amplification of positive-strand poliovirus RNA from the negative-strand template and, as with the majority of other host proteins involved in the infectious  cycles of picornaviruses, is a nuclear-resident protein. hnRNP C1 and C2 are produced by alternative splicing, with the C2 isoform containing 13 additional amino acids (Koloteva-Levine et al., 2002). Together, these hnRNP C1 and C2 proteins form a heterotetramer containing three copies of C1 and a single copy of C2 that bind pre-mRNA, regulate splicing, and nucleate the formation of 40S hnRNP particles (Barnett et al., 1989; Huang et al., 1994). Each C protein contains an RNA recognition motif, an oligomerization domain, a nuclear localization signal, and a nuclear retention signal (G?rlach et al., 1992; McAfee et al., 1996; Nakielny and Dreyfuss, 1996; Wan et al., 2001). In contrast to many other hnRNP proteins, hnRNP C1/C2 appears to be restricted to the nucleus and does not shuttle to the cytoplasm in complex with mRNA (Pi?ol-Roma and Dreyfuss, 1992, 1993). hnRNP C1/C2 can bind both the 3��- and 5��-termini of poliovirus [http://www.selleckchem.com/products/Vorinostat-saha.html Vorinostat mouse] negative-sense RNA intermediates (regions complementary to the 5��NCR and 3��NCR of genomic RNA, respectively) and has been proposed to play a role in poliovirus RNA replication  by facilitating and/or stabilizing the terminal strand separation required for replication of this template (Roehl and Semler,  1995; Brunner et al., 2005; Ertel et al., 2010). The association of hnRNP C1/C2 with both termini of the negative-sense RNA molecule may also allow for the end-to-end linkage of this RNA template via the multimerization of hnRNP C1/C2 tetramers, since the multimerization domain of this protein is required for efficient in vitro replication of poliovirus RNA (Ertel et al., 2010). Recombinant hnRNP C1/C2 is able to rescue positive-strand RNA synthesis in cellular extracts depleted of endogenous hnRNP C1/C2, supporting a critical role for this protein in the production of poliovirus genomic RNA (Brunner et al., 2005). It has also been demonstrated that hnRNP C1/C2 interacts with the poliovirus protein 3CD (the polymerase precursor) through glutathione S-transferase pull-down assays; therefore, hnRNP C1/C2 may aid in the recruitment of the 3D polymerase to the replication template (Brunner et al., 2005). Furthermore, reduced cellular levels of hnRNP C1/C2 cause a decrease in the kinetics of poliovirus RNA synthesis during infection (Brunner et al., 2010). Combined with the finding that an intact 3�� NCR of poliovirus genomic RNA contributes to positive-strand RNA synthesis efficiency through complementary elements conserved at the 5�� end of negative-sense strand, a model for positive-sense RNA synthesis has been proposed.