👤 Marsha DeSmet

The human papillomavirus (HPV) is a small, non-enveloped virus with a circular double-stranded DNA genome. The HPV genome encodes the E2 activator protein, which is required for viral transcription. R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals to duplex DNA. These structures form during papillomavirus transcription. We and others have demonstrated that resolution of viral R loops is crucial for HPV episomal maintenance. ZPR1 is a zinc finger protein that can recruit SETX to mammalian R-loops to mediate resolution. E2 binds to and recruits SETX, an R-loop helicase, to the viral promoter. We observed E2 in complex with SETX and ZPR1. However, we found that ZPR1 depletion decreased viral R-loops while enhancing cellular R-loops. ZPR1 depletion also increased SETX binding to the viral promoter. These data suggest that ZPR1 is not required for HPV R-loop resolution, in contrast to what has been observed in mammalian cells. We detected the E2 protein associated with R-loops and found that E2 overexpression increases cell-derived R-loop formation. Analysis of TCGA datasets revealed that ZPR1, but not SETX, mRNA expression is significantly reduced in HPV-positive cervical and head and neck cancers. Together, these findings indicate that while E2 mediates HPV R-loop resolution, it also promotes R-loop accumulation in the host genome, likely through SETX sequestration. Show less

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of guanosine triphosphate nucleotides. Among posttranslational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on the ER structure remains unclear. Here, we show that exostosin-1 (EXT1) glycosyltransferase, an enzyme involved in Show less