This Title All WIREs
How to cite this WIREs title:
Impact Factor: 9.957

Viral modulation of cellular RNA alternative splicing: A new key player in virus–host interactions?

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Abstract Upon viral infection, a tug of war is triggered between host cells and viruses to maintain/gain control of vital cellular functions, the result of which will ultimately dictate the fate of the host cell. Among these essential cellular functions, alternative splicing (AS) is an important RNA maturation step that allows exons, or parts of exons, and introns to be retained in mature transcripts, thereby expanding proteome diversity and function. AS is widespread in higher eukaryotes, as it is estimated that nearly all genes in humans are alternatively spliced. Recent evidence has shown that upon infection by numerous viruses, the AS landscape of host‐cells is affected. In this review, we summarize recent advances in our understanding of how virus infection impacts the AS of cellular transcripts. We also present various molecular mechanisms allowing viruses to modulate cellular AS. Finally, the functional consequences of these changes in the RNA splicing signatures during virus–host interactions are discussed. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing
Summary of the splicing reaction and regulatory signals/proteins involved. (a) The cycle of assembly and disassembly of the spliceosome throughout the splicing reaction. The stepwise interaction of the spliceosomal small ribonucleoprotein (snRNP) particles (U1, U2, U4, U4, U5, and U6; colored circles) in the excision of an intron from a pre‐mature RNA (pre‐mRNA) containing two exons (blue and gray) is depicted. The name of the spliceosomal complexes and the two catalytic steps of the reaction are indicated. (b) Positive and negative signals are stabilizing or destabilizing the assembly of the spliceosome on the pre‐mRNA by cis‐acting elements. The diagram represents a typical segment of eukaryotic precursor messenger RNA with one exon and the two surrounding introns. Intronic and exonic splicing enhancers (ISE and ESE; in green) are typically bound by factors promoting the splicing reaction from nearby splice sites, such as serine‐arginine repeats (SR) proteins. Intronic and exonic splicing silencers (ISS and ESS; in red) are typically bound by factors inhibiting splicing from nearby splice sites, such as heterogeneous nuclear ribonucleoprotein particle (hnRNP) proteins
[ Normal View | Magnified View ]
Schematic representation of the mechanisms of action for viral products that are potent modulators of cellular AS. NS5 from dengue virus, 3DPOL from picornavirus, NS1 from influenza virus, 2APRO from poliovirus, Vpr from HIV‐1 and ICP27 from Herpesviridae were all shown to interact with the spliceosome and inhibits the splicing reaction. SM and EBER1 from Epstein–Barr virus and ICP27 from herpes‐simplex virus 1 interact with splicing factors, and ICP27 is also able to interact with kinases that phosphorylate splicing factors. In the case of ICP27 which appears at numerous places in this figure, the mechanism of action sufficient to trigger a change in cellular AS is still not clear
[ Normal View | Magnified View ]
Summary of the different types of AS events and the biological role of AS. (a) Exon skipping, mutually exclusive exon and tandem exon cassette allow selective removal of complete exons from the mature RNA. Alternative 5′ and 3′ splice site selection allows removal of a part of an exon, either in 5′ or 3′ using the intron as the reference. An intron might be kept in the mature RNA, leading to intron retention. Gray boxes represent regions that are alternatively spliced; blue boxes represent regions that are always conserved in the mature mRNA; yellow boxes represent poly‐adenylation signals (PAS). TSS: Transcription start site. (b) The Bcl‐x pre‐mRNA is depicted, with the gray region (alternative 5′ splice site) being spliced in or out to give rise to the short (Bcl‐xS) or long (Bcl‐xL) isoforms. The former produces a pro‐apoptotic protein, and the latter an anti‐apoptotic one, underlining the importance of AS for the regulation of biological activities of proteins
[ Normal View | Magnified View ]

Related Articles

Virus-Host Interactions: The RNA Perspective

Browse by Topic

RNA Processing > Splicing Regulation/Alternative Splicing
RNA in Disease and Development > RNA in Disease

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts