Inhibition of HPV-16 L1 expression from L1 cDNAs correlates with the presence of hnRNP A1 binding sites in the L1 coding region.
The human papillomavirus type 16 (HPV-16) L1 capsid protein is very poorly expressed from cDNA expression plasmids transiently transfected into mammalian cells. The results described herein demonstrate that inhibition of HPV-16 L1 expression from L1 cDNAs correlates with the presence of splicing regulatory sequences in the L1 coding region. This inhibitory effect correlates with the binding of hnRNP A1 to the RNA elements. Similar to unutilised splice sites that may retain mRNAs in the nucleus, regulatory splicing RNA elements may also inhibit gene expression in the absence of splicing. The results presented here explain the inefficient expression of HPV-16 L1 protein from the wild type L1 cDNA expression plasmids in mammalian cells. These results may be of general interest since alteration of RNA sequences to prevent unwanted RNA-protein interactions may increase expression of many different genes in transient transfections or after plasmid uptake in DNA vaccination approaches.
Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Husargatan 3, Box 582, 751 23 Uppsala, Sweden.
Xiaomin
X
Zhao
Stefan
S
Schwartz
D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D015967:Gene Expression Regulation, Viral; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics*; D012326:RNA Splicing; D012367:RNA, Viral / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection
D036022:Capsid Proteins; D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; C063317:L1 protein, Human papillomavirus type 16