Viral RNPs, mRNA Stability and Export

非编码RNA在携带三种转化疱疹病毒的淋巴细胞中的作用 调查过了。爱泼斯坦-巴尔病毒(EBV)感染并转化人类B细胞；它是引起 传染性单核细胞增多症，与几种人类癌症有关。人类疱疹病毒(HVS)诱导 新大陆猴子的致命性淋巴瘤和白血病，并转化人和猴子的T淋巴细胞 在培养中，产生成熟的；激活的表型。卡波西肉瘤相关疱疹病毒 折磨免疫受损的个体，并以潜伏的形式持续存在，直到溶解激活。这两个EBVencode EBERs，以及新发现的23个microRNAs，以及7个人类免疫缺陷病毒编码的HSURs是 在病毒转化的细胞中表达。在诱导后，KSHV产生PAN，一种有帽的多腺化RNA 这并不会离开原子核。这些病毒RNA都很小(从21nts到1.1kb)，丰富，保守， 并与宿主蛋白结合形成RNPs。研究它们的功能已经做出了重要贡献 对宿主细胞途径的洞察在病毒转化或裂解生长过程中受到干扰。 提议的AIMS将检验EBERS、HSURS和PAN通过以下方式操纵细胞代谢的假设 隔离宿主蛋白或microRNAs，或由此产生的RNPs执行关键的病毒功能。我们 最近发现HSUR RNP与某些宿主microRNAs结合；干扰它们在 将对转化的T细胞进行检查。EBERs同样与宿主microRNA结合的可能性将是 测试过。我们的发现是，静止细胞中的microRNA激活而不是抑制翻译 利用来研究EBV编码的microRNA，因为许多转化的B细胞处于静止状态 身体里的状态。我们发现，在KSHV重新激活的情况下，PAN RNA积累到非常高的核水平 这是因为靠近其3‘端的一个元件(ENE)与Polya尾巴接合，以防止RNA衰退。结构性 对ENE+/-寡核苷酸以及与Polya结合蛋白(PABPC1)的络合作用的研究将提供 机械的洞察力。我们观察到PAN RNA参与了宿主PABPC1到 核，表明与宿主mRNA中的KSHV Sox蛋白的合作，将被调查

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