The RNA stability regulator HuR regulates L1 protein expression in vivo in differentiating cervical epithelial cells.
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.
Cumming
S A
SA
Faculty of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, 120 University Place, Glasgow G12 8TA, Scotland, UK.
Chuen-Im
T
T
Zhang
J
J
Graham
S V
SV
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*
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