Regulation of retroviral polyadenylation

Cellular and viral preRNAs are extensively cotranscriptionally modified. These modifications include the processing of the 3' end. Most preRNAs are polyadenylated, which is required for nuclear export, RNA stability, and efficient translation. Integrated retroviral genomes are flanked by 3' and 5' long terminal repeats (LTRs). Both LTRs are identical on the nucleotide level, but 3' processing has to be limited to the 3'LTR. Otherwise, polyadenylation at the 5'LTR would result in prematurely terminated, noncoding viral RNAs. Retroviruses have developed a variety of different mechanisms to restrict polyadenylation to the 3'LTR, although the overall structure of the LTRs is similar among all retroviruses. In general, these mechanisms can be divided into three main groups: (1) activation of polyadenylation only at the 3' end by encoding the essential polyadenylation signal in the unique 3 region; (2) suppression of polyadenylation at the 5'LTR by downstream elements such as the major splice donor; and (3) the usage of weak polyadenylation sites, which results in some premature polyadenylated noncoding RNAs and in read-through transcripts at the 3'LTR. All these mechanisms exhibit intrinsic problems, and retroviruses have evolved additional regulatory elements to promote polyadenylation at the 3'LTR only. In this review, we describe the molecular regulation of retroviral polyadenylation and highlight the different mechanisms used for polyadenylation control.