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Cherry, Jonathan Joseph

Microbiology and Molecular Genetics

2004

Ph. D.

Poly(A) site choice is highly regulated during gene expression. The coordination of mRNA processing factors is instrumental in the recognition of functional poly(A) sites and the silencing of cryptic sites. Poly(A) sites in HIV and the human dystrophin gene are silenced due to their positioning relative to the cap proximal 5' splice site. Recognition of these poly(A) sites is negatively influenced when factors within the U1 snRNP bind to a downstream poly(A) site. Splicing factors may also be involved in the enhancement of poly(A) site recognition. In the CT/CGRP gene, the splicing factors SRp20, U1-70k, and polypyrimidine tract binding protein (PTB) have been implicated in enhancement of an internal poly(A) site. In fact, we show that the RS domain of SRp20 can enhance cleavage and polyadenylation in vitro and poly(A) site choice in vivo. We believe that communication between splicing and 3' -end processing factors is vital to the regulation of gene expression. The orientation of these signals is important to poly(A) site recognition and likely represents a mechanism to prevent polyadenylation and expression of improperly processed transcripts.