Kaposi’s sarcoma-associated herpesvirus (KSHV) induces life-long infections and has evolved many ways to exert extensive control over its host’s transcriptional and post-transcriptional machinery to gain better access to resources and dampened immune sensing. The hallmark of this takeover is how KSHV reshapes RNA fate both to control expression of its own gene but also that of its host. From the nucleus to the cytoplasm, control of RNA expression, localization, and decay is a process that is carefully tuned by a multitude of factors and that can adapt or react to rapid changes in the environment. Intriguingly, it appears that KSHV has found ways to co-opt each of these pathways for its own benefit. Here we provide a comprehensive review of recent work in this area and in particular recent advances on the post-transcriptional modifications front. Overall, this review highlights the myriad of ways KSHV uses to control RNA fate and gathers novel insights gained from the past decade of research at the interface of RNA biology and the field of KSHV research.

Kaposi’s Sarcoma-associated herpesvirus (KSHV) is a herpesvirus that induces lifelong infection, and as such, its lytic replication is carefully controlled to allow for efficient dissemination from its long-term reservoir and for the spread of the virus to new hosts. Viral DNA replication involves many host and viral proteins, coordinating both in time and space to successfully progress through the viral life cycle.

Extensive remodeling of the host gene expression environment by coronaviruses nsp1 proteins is a well-documented and conserved piece of the coronavirus-host takeover battle. However, whether and how the underlying mechanism of regulation or the transcriptional target landscape differ amongst coronaviruses remains mostly uncharacterized. In this study we use comparative transcriptomics to investigate the diversity of transcriptional targets between four different coronavirus nsp1 proteins (from MERS, SARS1, SARS2 and 229E). In parallel, we performed Affinity Purification followed by Mass-Spectrometry to identify common and divergent interactors between these different nsp1. For all four nsp1 tested, we detected widespread RNA destabilization, confirming that both β- and α- Coronavirus nsp1 broadly affect the host transcriptome. Surprisingly, we observed that even closely related nsp1 showed little similarities in the clustering of genes targeted. Additionally, we show that the RNA targeted by nsp1 from the α-CoV 229E partially overlapped with MERS nsp1 targets. Given MERS nsp1 preferential targeting of nuclear transcripts, these results may indicate that these nsp1 proteins share a similar targeting mechanism. Finally, we show that the interactome of these nsp1 proteins differ widely. Intriguingly, our data indicate that the 229E nsp1, which is the smallest of the nsp1 proteins tested here, interacts with the most host proteins, while MERS nsp1 only engaged with a few host proteins. Collectively, our work highlights that while nsp1 is a rather well-conserved protein with conserved functions across different coronaviruses, its precise effects on the host cell is virus-specific.

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For over a decade, studies of messenger RNA regulation have revealed an unprecedented level of connectivity between the RNA pool and global gene expression. These connections are underpinned by a vast array of RNA elements that coordinate RNA-protein and RNA-RNA interactions, each directing mRNA fate from transcription to translation. Consequently, viruses have evolved an arsenal of strategies to target these RNA features and ultimately take control of the pathways they influence, and these strategies contribute to the global shutdown of the host gene expression machinery known as "Host Shutoff". This takeover of the host cell is mechanistically orchestrated by a number of non-homologous virally encoded endoribonucleases. Recent large-scale screens estimate that over 70 % of the host transcriptome is decimated by the expression of these viral nucleases. While this takeover strategy seems extraordinarily well conserved, each viral endonuclease has evolved to target distinct mRNA elements. Herein, we will explore each of these RNA structures/sequence features that render messenger RNA susceptible or resistant to viral endonuclease cleavage. By further understanding these targeting and escape mechanisms we will continue to unravel untold depths of cellular RNA regulation that further underscores the integral relationship between RNA fate and the fate of the cell.