AI Summary
Viruses rely on host cell functions for replication, and targeting these functions is a potential strategy for antiviral therapy. Alternative RNA splicing is exploited by many viruses, making them sensitive to splicing modulators. The SR family of proteins, involved in splicing regulation, is controlled by phosphorylation by various SR kinases. Studies have shown that SR kinases play a role in regulating viral replication.
INTRODUCTIONDue to their limited genome size, viruses depend on multiple host cell functions for gene expression and virion assembly/release (1). If viruses from diverse taxonomic groups are dependent on the same cellular process, modulating the process offers an alternative strategy to inhibit virus replication and generate broad-spectrum anti-virals (1). Many viruses exploit alternative RNA splicing to expand their coding capacity, rendering them sensitive to splicing modulators (2 – 5). In addition to the core components of the host splicing apparatus, the serine-arginine-rich (SR) family of proteins plays an important role in the regulation of gene expression by controlling constitutive and alternative splicing (AS) of RNAs (6). Besides their known roles in spliceosome assembly and splice-site recognition (7), SR proteins also have been implicated in the regulation of transcription, polyadenylation, export of mRNA, RNA stability, and translation (6, 8). The activity and localization of SR proteins are controlled by their phosphorylation by a variety of SR kinases (9, 10) including serine/arginine-specific protein kinases (SRPKs), Cdc2-like kinases (CLKs), and dual-specificity tyrosine-regulated kinases (DYRKs), all sharing the common property of phosphorylating SR proteins at the serine residues within their RS (arginine-serine rich) region (7, 11, 12). Several studies have demonstrated that SR kinases have a role in regulating viral replication via direct or indirect mechanisms (phosphorylation/dephosphorylation of cellular and/or viral targets, cellular response to viral infection) (5, 6, 13, 14). Interestingly, SR kinases and their substrates influence not only viruses that replicate in the nucleus [HIV-1, influenza, and adenovirus (5, 13)] but