Abstract
BackgroundDuring reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal.ResultsHere, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation.ConclusionRecently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5’end of their RNA. At the 3’end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression.
Highlights
During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs)
In cells transfected with the pHSRV13-SDm1 plasmid, neither gag-encoding genomic RNA nor pol or env RNA was retrieved (Figure 1C, lane 5), indicating that the mutation in SDm1 might activate cleavage and polyadenylation similar to inactivation of the human immunodeficiency virus type 1 (HIV-1) major splice donor (MSD) [16,18]
We recently showed that a mechanism similar to that of suppression of polyadenylation at the 5′LTR of Foamy virus (FV) is the origin of an inherited immunodeficiency syndrome [34]
Summary
Retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. Polyadenylation (poly(A)) is provided, by four sequence elements: the polyadenylation signal (poly(A) signal), the cleavage site (poly(A) site), G/U-rich downstream elements (DSE), and upstream cleavage factor I binding sites (for review see [1,2,3,4]). Retroviruses use novel mechanisms to control polyadenylation and serve as useful tools to study regulation of this produced, while suppression of poly(A) addition would result in suppression of full-length transcripts. The regulation of retroviral polyadenylation appears to depend on cellular factors and on viral RNA sequences, as no retroviruses have been shown to encode proteins that impact polyadenylation. Three different types of retroviral mechanisms for polyadenylation regulation have been identified (for review see [5])
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