The human papillomavirus type 16 negative regulatory RNA element interactswith three proteins that act at different posttranscriptional levels

In human papillomaviruses, expression of the late genes L1 and L2, encoding the capsid proteins, is restricted to the upper layers of the infected epi thelium. A 79-nt GU-rich negative regulatory element (NRE) located at the 3 ' untranslated region of the human papillomavirus 16 L1 gene was identified previously as key to the posttranscriptional control of late gene expressi on. Here, we demonstrate that in epithelial cells, the NRE can directly bin d the U2 auxiliary splicing factor 65-kDa subunit, the cleavage stimulation factor 64-kDa subunit, and the Elav-like HuR protein. On induction of epit helial cell differentiation, levels of the U2 auxiliary splicing factor 65- kDa subunit decrease, levels of the cleavage stimulation factor 64-kDa subu nit increase, and the levels of HuR remain unchanged, although redistributi on of the HuR from the nucleus to the cytoplasm is observed. Late gene tran scripts, which appear to be fully processed, are detected in undifferentiat ed W12 cells, but are confined in the nucleus. We propose that repression o f late gene expression in basal epithelial cells may be caused by nuclear r etention or cytoplasmic instability of NRE-containing late gene transcripts .