Strength in Diversity: Nuclear Export of Viral RNAs

Abstract

The nuclear export of cellular mRNAs is a complex process that requires the orchestrated participation of many proteins that are recruited during the early steps of mRNA synthesis and processing. This strategy allows the cell to guarantee the conformity of the messengers accessing the cytoplasm and the translation machinery. Most transcripts are exported by the exportin dimer Nuclear RNA export factor 1 (NXF1)–NTF2-related export protein 1 (NXT1) and the transcription–export complex 1 (TREX1). Some mRNAs that do not possess all the common messenger characteristics use either variants of the NXF1–NXT1 pathway or CRM1, a different exportin. Viruses whose mRNAs are synthesized in the nucleus (retroviruses, the vast majority of DNA viruses, and influenza viruses) exploit both these cellular export pathways. Viral mRNAs hijack the cellular export machinery via complex secondary structures recognized by cellular export factors and/or viral adapter proteins. This way, the viral transcripts succeed in escaping the host surveillance system and are efficiently exported for translation, allowing the infectious cycle to proceed. This review gives an overview of the cellular mRNA nuclear export mechanisms and presents detailed insights into the most important strategies that viruses use to export the different forms of their RNAs from the nucleus to the cytoplasm.

RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling

“…DDX3 interacts with CRM1 through a NES relocating DDX3 into the cytoplasm (Figure 2a) [23,28]. Of note, as will be discussed below, the interaction between DDX3 and CRM1 is exploited by HIV-1 to favor the cytoplasmic accumulation of intron-containing viral RNA [29][30][31]. Another aspect of mRNA metabolism in which DDX3 has been involved is translation, specifically at the initiation step.…”

Epigenetic Dysregulations in Merkel Cell Polyomavirus-Driven Merkel Cell Carcinoma

“…NCCR consists of the viral DNA replication origin, and early and late promoters/enhancers [ 25 , 27 ]. The early and late regions regulate early and late gene expression, respectively [ 28 ]. The early genes encode for transcripts generated by alternative splicing, such as LT and sT, 57 kT, and ALTO [ 29 , 30 , 31 ].…”

Nuclear export of plant pararetrovirus mRNAs involves the TREX complex, two viral proteins and the highly structured 5′ leader region

“…Like all living organisms, yeast, plants and metazoa are exposed to diverse viral infections. Many DNA and RNA viruses with nuclear replication steps in their life cycles export viral mRNAs by hijacking the TAP/p15 pathway ( 36 ). Herpesviruses, in which most mRNAs are intronless, have evolved highly efficient mechanisms for their maturation and export.…”