Role of hnRNP A1 in coronavirus RNA synthesis.

Abstract

Several host proteins have been identified that bind to the cis-acting sequences of mouse hepatitis virus (MHV) RNAs (Furuya and Lai, 1993; Yu and Leibowitz, 1995; Zhang and Lai, 1995; Li et al., 1997, 1999). The first among those is the heterogeneous nuclear ribonucleoprotein (hnRNP) Al. In normal mammalian cells, hnRNP-Al is predominantly localized in the nucleus, but it shuttles between the nucleus and the cytoplasm (Dreyfuss et al., 1993). It interacts with a number of RNAs, particularly pre-mRNA and snRNAs, and a number of proteins such as itself, other hnRNPs and some serine-arginine (SR)-rich proteins through its amino terminal RNA-binding domains and the carboxyl terminal glycine-rich domain, respectively, and thus is associated with the RNP complex (Dreyfuss et al. 1993; Buvoli et al., 1988; Cartegni et al., 1996). hnRNP A1 has been implicated in promoting RNA-reannealing (Buvoli et al., 1992) and in regulating alternative RNA-splicing (Dreyfuss et al., 1993). Its involvement in regulation of viral RNA processing of human immunodeficiency virus (HIV) and human T-cell leukemia virus (HTLV)-2 has also been suggested (Black et al, 1995, 1996). Recent evidence indicates that hnRNP Al is required for inhibition of HIV-1 pre-mRNA splicing (Caputi et al., 1999). Previously, we found that hnRNP Al specifically binds to the cis-acting sequences (the negative-strand leader and intergenic [IG] sequence) of MHV RNA (Furuya and Lai, 1993; Zhang and Lai, 1995). Site-directed mutagenesis of the IG sequence indicated that the extent of mRNA transcription correlates with the efficiency of hnRNP A1-binding to the IG sequence (Zhang and Lai, 1995). In MHV-infected cells, hnRNP A1 is translocated from the nucleus to the cytoplasm (Li et al., 1997). These findings suggest that hnRNP Al may play a role in regulation of MHV RNA replication and transcription. However, to date, no direct evidence for a functional role of hnRNP Al in MHV RNA synthesis has been reported.KeywordsHelper VirusRecombinant Vaccinia VirusHeterogeneous Nuclear RibonucleoproteinMouse Hepatitis VirusIntracellular Viral RNAsThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.