The early noncoding region of human papillomavirus type 16 is regulated by cytoplasmic polyadenylation factors

Abstract

All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3′ untranslated region (3′UTR). The 3′end of the early E5 open reading frame and the 3′UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (CPEs). We show here that a fragment of the early 3′end comprising four of the five CPE-like regions when inserted downstream of a reporter gene confers regulation of the gene expression. A key protein involved in cytoplasmic polyadenylation is CPEB. We show that the human CPEB1 can repress the activity of the reporter construct containing the HPV-16 early sequences. This repression can be counteracted by a human cytoplasmic poly(A) polymerase, hGLD-2 fused to CPEB1. The hGLD-2/CPEB1 fusion protein facilitates furthermore poly(A) elongation of early HPV transcripts.