Abstract
Eukaryotic mRNA 3´-end processing is a multi-step process beginning with pre-mRNA transcript cleavage followed by poly(A) tail addition. Closely coupled to transcription termination, 3´-end processing is a critical step in the regulation of gene expression, and disruption of 3´-end processing is known to affect mature mRNA levels. Various viral proteins interfere with the 3´-end processing machinery, causing read-through transcription and altered levels of mature transcripts through inhibition of cleavage and polyadenylation. Thus, disruption of 3´-end processing contributes to widespread host shutoff, including suppression of the antiviral response. Additionally, observed features of read-through transcripts such as decreased polyadenylation, nuclear retention, and decreased translation suggest that viruses may utilize these mechanisms to modulate host protein production and dominate cellular machinery. The degree to which the effects of read-through transcript production are harnessed by viruses and host cells remains unclear, but existing research highlights the importance of host 3´-end processing modulation during viral infection.
Highlights
This review describes many of the known effects of certain viruses on RNA 3 ́-end processing and transcription termination, including read-through transcription induced by influenza A protein NS1 and herpes simplex virus-1 (HSV-1) protein ICP27
Reduced binding of symplekin, a protein that typically associates with the 3 ́-end processing machinery, to cleavage and polyadenylation specificity factor (CPSF) was observed in the presence of ICP27 [48]. These findings indicate that ICP27 may interfere with assembly of the canonical CPSF complex, leading to disruption of cleavage and polyadenylation
Influenza viruses containing NS1 proteins with mutated CPSF binding sites displayed relief of inhibition of host mRNA production for several examined genes as well as restoration of mRNA 3 ́-end cleavage [40, 58, 59]. These results collectively suggest that NS1 binding to CPSF and consequent disruption of host 3 ́-end processing and termination within the infected cell negatively regulates host gene expression on a global scale
Summary
Various viral proteins interfere with the 3 ́-end processing machinery, causing read-through transcription and altered levels of mature transcripts through inhibition of cleavage and polyadenylation. This review describes many of the known effects of certain viruses on RNA 3 ́-end processing and transcription termination, including read-through transcription induced by influenza A protein NS1 and herpes simplex virus-1 (HSV-1) protein ICP27.
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