The retrovirus RNA trafficking granule: from birth to maturity

Abstract

Post-transcriptional events in the life of an RNA including RNA processing, transport, translation and metabolism are characterized by the regulated assembly of multiple ribonucleoprotein (RNP) complexes. At each of these steps, there is the engagement and disengagement of RNA-binding proteins until the RNA reaches its final destination. For retroviral genomic RNA, the final destination is the capsid. Numerous studies have provided crucial information about these processes and serve as the basis for studies on the intracellular fate of retroviral RNA. Retroviral RNAs are like cellular mRNAs but their processing is more tightly regulated by multiple cis-acting sequences and the activities of many trans-acting proteins. This review describes the viral and cellular partners that retroviral RNA encounters during its maturation that begins in the nucleus, focusing on important events including splicing, 3' end-processing, RNA trafficking from the nucleus to the cytoplasm and finally, mechanisms that lead to its compartmentalization into progeny virions.

Figure 1

Model for NRS effects on splicing and polyadenylation. Schematic of RSV RNA with exons depicted as boxes and introns shown as thin lines. The light shading represents the upstream SR protein binding region of the bipartite NRS, and the darker shading depicts the region that binds U1 snRNP. SR proteins promote U1 binding, which initiates early interactions with factors associated with the viral 3' splice site (env in this example), and this is thought to mature into a spliceosome-like NRS inhibitory complex (indicated by the large oval) that forms between the NRS and the viral 3' splice site but which is catalytically inactive (an X over the intron); a possible role for U6 snRNP is indicated by the question mark. The NRS complex sequesters the 3'ss from interacting with the authentic viral 5'ss to block splicing. The NRS complex may influence polyadenylation by serving to stabilize the binding of splicing factors to the weak viral 3' splice site, which can then either recruit or stabilize the polyadenylation complex (arrow) and thereby enhance polyadenylation of viral unspliced RNA. U11 snRNP modulates NRS function by antagonizing U1 binding and assembly of the NRS inhibitory complex. A downstream region (intermediate shading) binds hnRNP H, which recruits U11 to a site that overlaps the U1 binding site.

Figure 2

Processing of HIV-1 RNA. Outlined in the figure are the cis-acting components of the HIV-1 RNA which control its processing. Indicated are the positions of the 5' splice sites (arrows above the unspliced RNA), 3' splice sites (brackets below the unspliced RNA), and the various ESS and ESE elements that modulate splice site use. At top is an outline of viral genome and on the bottom, the exons which comprise the major spliced forms (4.0 kb singly spliced and 1.8 kb multiply spliced) of the genomic RNA are indicated by black boxes. Multiple spliced RNAs combining or excluding various exons encode each of the viral accessory proteins.