title: Specific interaction between hnRNP H and HPV16 L1 proteins: implications for late gene auto-regulation enabling rapid viral capsid protein production.
abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulating the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.
authors.affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005, PR China.
authors.forename: Zi-Zheng
authors.initials: ZZ
authors.lastname: Zheng
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
authors.forename: Ji
authors.initials: J
authors.lastname: Miao
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D001483:Base Sequence; D036022:Capsid Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D025461:Feedback, Physiological; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16