机构地区: 北京工业大学生命科学与生物工程学院
出 处: 《中国生物化学与分子生物学报》 2010年第10期886-891,共6页
摘 要: TARRNA结合蛋白是细胞中双链RNA结合蛋白家族成员之一.它可以结合HIV-1TARRNA,并与Tat协同作用激活LTR表达,进而促进病毒的转录与翻译.TRBP也是将干扰素抗病毒通路与RNA干扰免疫通路相连的一种细胞蛋白.在干扰素诱生的PKR反应中,TRBP通过直接抑制PKR的自磷酸化、与PKR竞争通用的RNA底物或与PACT形成异源二聚体等机制抑制细胞内的PKR反应,从而降低了PKR介导的对病毒表达的抑制作用.TRBP与Dicer和Ago2等组成的RNA诱导沉默复合体,在RNA干扰中发挥着关键作用并调控随后的序列特异性降解.在HIV-1感染中,TRBP更倾向于促进病毒的表达与复制,因此TRBP也成为控制HIV-1感染的新靶点. Transactivation response RNA binding protein (TRBP),which binds to HIV-1 TAR RNA, belongs to the dsRNA binding protein family.TRBP promotes the expression of HIV-1 LTR by activating the basal transcription level of HIV-1 LTR or contributing to Tat-mediated transactivation.TRBP increases the efficiency of HIV-1 genes transcription and translation after binding to TAR RNA.TRBP is also a cellular protein linking the interferon anti-viral pathway and RNA interference pathway as an immune regulator.In interferon-induced PKR response,TRBP reverses the PKR inhibition of HIV-1 expression and production.TRBP acts as a cellular down-regulator of PKR by directly inhibiting PKR autophosphorylation,by competing for common RNA substrates with PKR,or by forming heterodimers with PACT.TRBP recruits the Dicer complex to Ago2 constituting the critical component of the RNA induced silencing complex (RISC ),which is a key complex in the RNA interference pathway that controls the subsequent sequence-specific mRNA degradation.During HIV-1 infection,TRBP is prone to augment HIV-1 expression and replication, indicating that TRBP is a novel therapeutic target for controlling HIV-1 infection.