Destiny of Unspliced Retroviral RNA: Ribosome and/or Virion?

Abstract

A longstanding unknown in viral RNA biology is the relationship between translation and packaging of genomic RNA. For retroviruses, an extensive body of work has characterized nuclear export of the unspliced genome-length transcript (5,8,15), but the cytoplasmic trafficking of the RNA has remained relatively undefined. An elegant experimental approach that was initiated over 25 years ago has been updated and extended to human retroviruses during the last year. A consensus on the relationship between translation and packaging of retroviral RNA has been reached. An unexpected finding was that retroviruses have adapted two divergent approaches to manage the cytoplasmic fate of genomic RNA. This minireview introduces the interdependent relationship between translation and packaging of retroviral RNA, postulates models of retroviral RNA trafficking in the cytoplasm, summarizes experimental results that address the models, and discusses the recent consensus.Unspliced genome-length retroviral RNA is utilized for both translation and packaging. Retroviruses are a unique family of RNA viruses that utilize virally encoded reverse transcriptase (RT) to replicate genomic RNA through a proviral DNA intermediate (40). The provirus is permanently integrated into the host cell chromosome and, like a cellular gene, is expressed by the host cell transcription, RNA processing, and translation machinery. The primary transcription product interacts with the cellular RNA processing machinery and, similar to a typical cellular pre-mRNA, is spliced, exported to the cytoplasm, and translated by the host protein synthesis machinery. A proportion of the pre-mRNA subverts typical RNA processing and interacts with viral and/or cellular nucleocytoplasmic shuttle proteins that activate nuclear export, despite the lack of intron removal (8). In the cytoplasm, the unspliced genome-length

The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

“…Retroviral gRNAs are capped and polyadenylated like mRNAs, and gRNAs and gagpol mRNAs are indistinguishable in primary sequence. How, where, or whether unspliced RNAs are partitioned into genome and mRNA functions is still unclear and probably differs among retroviruses (25, 41,70,312).…”

Cytoplasmic Utilization of Human Immunodeficiency Virus Type 1 Genomic RNA Is Not Dependent on a Nuclear Interaction with Gag

“…In particular, there is evidence for the existence of a single pool of HIV-1 gRNAs for translation and encapsidation (11). Dimerization of the gRNAs occurs in the cytoplasm prior to encapsidation (45,46).…”

RU5 of Mason-Pfizer Monkey Virus 5′ Long Terminal Repeat Enhances Cytoplasmic Expression of Human Immunodeficiency Virus Type 1 gag-pol and Nonviral Reporter RNA

“…By contrast, retroviral premRNA recruits viral or cellular posttranscriptional modulators that activate efficient nuclear export and cytoplasmic expression despite lack of intron removal (2,12,25,44). Once in the cytoplasm, the unspliced viral transcript exhibits dual function as mRNA template for translation of Gag precursor protein and Gag-Pol polyprotein and as genomic RNA that is packaged into progeny virions (6). The RNA packaging signal is a series of RNA structural motifs within the 5Ј untranslated region (UTR) that are recognized by the Gag nucleocapsid protein, which directs assembly of the unspliced RNA into progeny virions (1,35).…”