Functional interplay between viral and cellular SR proteins in control of post-transcriptional gene regulation

Abstract

Viruses take advantage of cellular machineries to facilitate their gene expression in the host. SR proteins, a superfamily of cellular precursor mRNA splicing factors, contain a domain consisting of repetitive arginine/serine dipeptides, termed the RS domain. The authentic RS domain or variants can also be found in some virus-encoded proteins. Viral proteins may act through their own RS domain or through interaction with cellular SR proteins to facilitate viral gene expression. Numerous lines of evidence indicate that cellular SR proteins are important for regulation of viral RNA splicing and participate in other steps of post-transcriptional viral gene expression control. Moreover, viral infection may alter the expression levels or modify the phosphorylation status of cellular SR proteins and thus perturb cellular precursor mRNA splicing. We review our current understanding of the interplay between virus and host in post-transcriptional regulation of gene expression via RS domain-containing proteins.

Figure 1

Viral SR proteins. The diagram shows domain structures of the representative viral proteins containing either a canonical RS domain (red) or an R/S‐rich motif (green). In the HBV core protein, three SPRRR motifs are underlined. Phosphorylation of the highlighted serine and threonine residues has been reported (see the text). Different highlights in the DHBV core protein represent different phosphorylation sites determined by three independent studies (see the text). The coronavirus (SARS‐CoV) nucleocapsid protein contains multiple phosphorylation sites (see the text); the two highlighted residues serve as the major phosphorylation sites of SRPK1 in vitro [12].

Figure 2

Viral and host gene expression is modulated through the interplay between viral proteins and cellular SR proteins. (A) Viral SR proteins (rectangle) recruit cellular SR proteins (oval) to promote splicing efficiency and/or modulate alternative splicing of viral transcripts. (B) Phosphorylation of viral proteins in the S/R‐rich motif may modulate their function and thereby influence viral and cellular activities. (C) Non‐SR viral proteins (rectangle) may interact directly with cellular SR proteins (purple oval) or modulate their phosphorylation status via SR protein kinases or phosphatases (green oval) and thereby determine the splicing patterns of both viral and cellular RNAs. In general, viral infection may influence the cellular splicing machinery, particularly SR proteins, thereby altering viral and host cell gene expression at the post‐transcriptional level.