My lab studies retroviral gene expression at the post-transcriptional level. An unusual feature of all retroviruses is that their primary RNA transcript is both a major viral mRNA, encoding capsid proteins, and a pre-mRNA. In addition, this unspliced RNA is packaged into viral particles as genomic RNA. We study control of retroviral RNA splicing, stability, and export. We have identified a Negative Regulator of Splicing (NRS) RNA element within the avian retroviral RNA intron, which helps maintain a portion of the primary transcripts as unspliced mRNA and genomic RNA. We are currently exploring the 3D structure of the NRS RNA (see Figure below) and the mechanism of its splicing suppression. The NRS behaves like a defective 5' splice site, binding all of the splicing snRNPs, and interacting with 3' splice sites. It appears to compete with the authentic 5' splice site for interactions with 3' splice sites. While the NRS pseudo-spliceosome contains all of the splicing snRNPs, their arrangement is aberrant. We have observed the pRP8 splicing scaffold protein is not localized in the pseudo-spliceosome. Recently, we have also found that the NRS promotes polyadenylation in vitro.
Rna transcription Rna Splicingg