title: The RNA stability regulator HuR regulates L1 protein expression in vivo in differentiating cervical epithelial cells.
abstract: Human papillomavirus (HPV) L1 and L2 capsid protein expression is restricted to the granular layer of infected, stratified epithelia and is regulated at least partly at post-transcriptional levels. For HPV16, a 79 nt late regulatory element (LRE) is involved in this control. Using W12 cells as a model for HPV16-infected differentiating cervical epithelial cells we show that HuR, a key cellular protein that controls mRNA stability, binds the LRE most efficiently in nuclear and cytoplasmic extracts of differentiated cells. Further, HuR binds the 3' U-rich portion of the LRE directly in vitro. Overexpression of HuR in undifferentiated W12 cells results in an increase in L1 mRNA and protein levels while siRNA knock-down of HuR in differentiated W12 cells depletes L1 expression. In differentiated cervical epithelial cells HuR may bind and stabilise L1 mRNAs aiding translation of L1 protein.
authors.affiliation: Faculty of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, 120 University Place, Glasgow G12 8TA, Scotland, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Cumming
authors.forename: T
authors.initials: T
authors.lastname: Chuen-Im
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: S V
authors.initials: SV
authors.lastname: Graham
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D036022:Capsid Proteins / Q000096:biosynthesis*; D002460:Cell Line; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D018628:Gene Dosage; D020868:Gene Silencing; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D036022:Capsid Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C063317:L1 protein, Human papillomavirus type 16