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Viral RNPs, mRNA Stability and Export

病毒 RNP、mRNA 稳定性和输出

基本信息

批准号：
7726050
负责人：
JOAN A. STEITZ
金额：
$ 18.36万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7726050
关键词：
3&apos Untranslated Regions Antibodies Antinuclear Antibodies B-Lymphocytes Binding Binding Proteins Biological Assay Callithrix Cancer Etiology Cebidae Cell Line Cell Nucleus Cells Collaborations Complex Elements Epstein-Barr virus encoded RNA 1 Epstein-Barr virus encoded RNA 2 Exhibits Functional RNA Gene Expression Growth Herpesviridae Homologous Gene Human Human Herpesvirus 4 Human Herpesvirus 8 Immunocompromised Host Immunofluorescence Immunologic In Vitro Individual Infection Infectious Mononucleosis Left Length Luciferases Lymphoid Cell Lymphoma Lytic Lytic Phase Malignant Neoplasms Messenger RNA Metabolism MicroRNAs Molecular Monkeys NMR Spectroscopy Nuclear Nuclear RNA Nucleotides Pathway interactions Phenotype Poly(A)+ RNA Primates Proteins RNA RNA Decay RNA Splicing Reporter Repression Resistance Resolution Ribonucleoproteins Roentgen Rays Role Saimiriine Herpesvirus 2 Site Small RNA Structure T-Lymphocyte Tail Testing Therapeutic Translational Repression Translations Untranslated Regions Viral Viral Physiology Virus X-Ray Crystallography antigen binding base cell transformation combat design gammaherpesvirus gene function in vivo insight leukemia/lymphoma mRNA Stability metaplastic cell transformation novel prevent sarcoma translation factor viral RNA

项目摘要

The roles of non-coding RNAs in lymphoid cells harboring three transforming herpesviruses are being investigated. Epstein-Barr virus (EBV) infects and transforms humanB cells; it is the causative agent of infectious mononucleosis and is associated with several human cancers. Herpesvirus saimiri (HVS) induces fatal lymphomas and leukemias in New World monkeys and transforms human and monkey T lymphocytes in culture, generating a mature; activated phenotype. Kaposi's sarcoma-associated herpesvirus (KSHV) afflicts immunocompromised individuals and persists in a latent form until lytic activation. The two EBVencoded EBERs, as well as >23 newly identified microRNAs, and the seven HVS-encoded HSURs are expressed in virally transformed cells. Upon induction, KSHV produces PAN, a capped, polyadenylated RNA that does not leave the nucleus. These viral RNAs are all small (from 21 nts to 1.1 kb), abundant, conserved, and associate with host proteins to form RNPs. Studying their functions has,already contributed important insights into host cell pathways perturbed during viral transformation or lytic growth. Proposed aims will test the hypotheses that EBERs, HSURs and PAN manipulate cellular metabolism by sequestering host proteins or microRNAs, or that the resulting RNPs perform a critical viral function. We recently found that HSUR RNPs bind certain host microRNAs; interference with their regulatory roles in transformed T cells will be examined. The possibility that EBERs likewise bind host microRNAs will be tested. Our discovery that microRNAs in quiescent cells activate rather than repress translation will be exploited to investigate the EBV-encoded microRNAs since many transformed B cells exist in a quiescent state in the body. We showed that PAN RNA accumulates to very high nuclear levels in KSHV-reactivated cells because an element (the ENE) near its 3' end engages the polyA tail to prevent RNA decay. Structural studies of the ENE +/- oligoA, as well as complexed with polyA binding protein (PABPC1), will provide mechanistic insights. Our observation that PAN RNA is involved in relocalization of host PABPC1 to the nucleus, suggesting collaboration with the KSHV SOX protein in host mRNA shut off, will be investigated

非编码rna在携带三种转化疱疹病毒的淋巴样细胞中的作用正在研究中