Regulation of the Human Papillomavirus Life Cycle by the Long Noncoding RNA DINO

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Karl  Munger
Organization: TUFTS UNIVERSITY BOSTON
Fiscal Year: 2023
Award: $418,426
Funding agency: National Institute of Allergy and Infectious Diseases

Despite the currently available effective prophylactic vaccines, human papilloma virus infections remain the most common cause of venereal disease. Human papilloma virus-associated diseases are particularly prevalent in medically underserved segments of the population. Despite decades of research, there are no strategies that can limit the spread of human papilloma viruses. The productive viral life cycle of these viruses has been studied extensively, but research has almost exclusively focused on the contributions of viral and cellular proteins and protein-coding mRNAs. However, most of the cellular transcriptome does not encode proteins. Some non-coding RNAs likely represent functionally irrelevant transcriptional noise but several classes of non-coding RNAs serve important regulatory functions. Long non-coding RNAs have only recently emerged as critical modulators of many cellular regulatory circuits. Human papilloma viruses replicate their genomes to high copy numbers and generate progeny virus in terminally differentiated epithelial cells. We showed that expression of the long non-coding RNA DINO increases during epithelial differentiation and that ectopic expression of the long noncoding RNA DINO in a patient-derived, human papillomavirus episome- containing cell line causes an increase in viral genomes. This proposal addresses the hypothesis that DINO plays a previously unanticipated role in regulating the differentiation-dependent life cycle of human papillomaviruses. We will deploy a combination of biochemical, cell and molecular biology approaches to define the biological activities of DINO in human papillomavirus genome replication in dividing and differentiated viral episome-containing, patient-derived cell lines. The results from our studies will yield novel molecular insights into the differentiation-dependent life cycle of human papillomaviruses.

Terms: <Acute><Address><Antioncogene Protein p53><Area><Biochemical><Biological><Buccal Mucosa><Cancer Cause><Cancer Etiology><Cancers><Cell Body><Cell Communication and Signaling><Cell Differentiation><Cell Differentiation process><Cell Growth in Number><Cell Line><Cell Multiplication><Cell Proliferation><Cell Signaling><CellLine><Cells><Cellular Proliferation><Cellular Tumor Antigen P53><Cellular biology><Code><Coding System><Country><DNA Damage><DNA Damage Repair><DNA Injury><DNA Molecular Biology><DNA Repair><Data><Development><Disease><Disorder><Ectopic Expression><Episome><Epithelial Cells><Epithelium><Functional RNA><Gene Transcription><Genetic Alteration><Genetic Change><Genetic Transcription><Genetic defect><Genome><Goals><HNSCC><HPV><HPV infection><Head and Neck Carcinoma><Head and Neck Squamous Cell Carcinoma><Human><Human Papilloma Virus><Human Papillomavirus><Human papilloma virus infection><Human papillomavirus infection><Immune response><Immunological response><Incidence><Individual><Infection><Infectious Human Wart Virus><Intracellular Communication and Signaling><Length><Lesion><Life Cycle><Life Cycle Stages><Maintenance><Malignant><Malignant - descriptor><Malignant Cell><Malignant Neoplasms><Malignant Tumor><Marketing><Mediating><Medical><Messenger RNA><Metabolic stress><Modern Man><Molecular><Molecular Biology><Mouth Mucosa><Mutation><Noise><Non-Coding><Non-Coding RNA><Non-Polyadenylated RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Oncoprotein p53><Oral Mucosa><Oral mucous membrane structure><Output><P53><Papilloma Viruses><Papillomaviridae><Papillomavirus><Patients><Phosphoprotein P53><Phosphoprotein pp53><Play><Population><Predisposition><Preventative vaccine><Preventive vaccine><Productivity><Prophylactic vaccine><Protein TP53><Proteins><Publishing><RNA><RNA Expression><RNA Gene Products><RNA Seq><RNA sequencing><RNAseq><Regulation><Research><Ribonucleic Acid><Role><SCCHN><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Signal Transduction><Signal Transduction Systems><Signaling><Site><Solid><Stimulus><Strains Cell Lines><Structure><Susceptibility><TP53><TP53 gene><TRP53><Testing><Transcription><Tumor Protein p53><Tumor Protein p53 Gene><Undifferentiated><Unscheduled DNA Synthesis><Untranslated RNA><Vaccinee><Vaccines><Venereal Diseases><Venereal Disorders><Venereal Infections><Viral><Viral Genome><Virus><biologic><biological signal transduction><cancer cell><cell biology><cellular targeting><chemotherapy><chronic infection><combat><cultured cell line><developmental><experiment><experimental research><experimental study><experiments><genome mutation><global gene expression><global transcription profile><head and neck squamous carcinoma><head and neck squamous cell cancer><host response><immune system response><immunoresponse><insight><keratinocyte><keratinocyte differentiation><life course><loss of function><mRNA><malignancy><medically under served><medically underserved><mutant><neoplasm/cancer><noncoding><novel><oral mucosae><oral mucosal><p53 Antigen><p53 Genes><p53 Tumor Suppressor><persistent infection><protein p53><response><social role><transcriptome><transcriptome sequencing><transcriptomic sequencing><transcriptomics><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><virus genome><wart virus>