Tian Chunjuan, Wang Tao, Zhang Wenyan, Yu Xiao-Fang
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Nucleic Acids Res. 2007;35(21):7288-302. doi: 10.1093/nar/gkm816. Epub 2007 Oct 24.
Diverse retroviruses have been shown to package host SRP (7SL) RNA. However, little is known about the viral determinants of 7SL RNA packaging. Here we demonstrate that 7SL RNA is more selectively packaged into HIV-1 virions than are other abundant Pol-III-transcribed RNAs, including Y RNAs, 7SK RNA, U6 snRNA and cellular mRNAs. The majority of the virion-packaged 7SL RNAs were associated with the viral core structures and could be reverse-transcribed in HIV-1 virions and in virus-infected cells. Viral Pol proteins influenced tRNAlys,3 packaging but had little influence on virion packaging of 7SL RNA. The N-terminal basic region and the basic linker region of HIV-1 NCp7 were found to be important for efficient 7SL RNA packaging. Although Alu RNAs are derived from 7SL RNA and share the Alu RNA domain with 7SL RNA, the packaging of Alu RNAs was at least 50-fold less efficient than that of 7SL RNA. Thus, 7SL RNAs are selectively packaged into HIV-1 virions through mechanisms distinct from those for viral genomic RNA or primer tRNAlys,3. Virion packaging of both human cytidine deaminase APOBEC3G and cellular 7SL RNA are mapped to the same regions in HIV-1 NC domain.
多种逆转录病毒已被证明会包装宿主信号识别颗粒(7SL)RNA。然而,关于7SL RNA包装的病毒决定因素却知之甚少。在此我们证明,相较于其他丰富的由RNA聚合酶III转录的RNA,包括Y RNA、7SK RNA、U6小核仁RNA(snRNA)和细胞信使RNA(mRNA),7SL RNA更具选择性地被包装进HIV-1病毒颗粒中。大多数病毒颗粒包装的7SL RNA与病毒核心结构相关,并且能够在HIV-1病毒颗粒以及病毒感染的细胞中发生逆转录。病毒聚合酶蛋白影响tRNAlys,3的包装,但对7SL RNA的病毒颗粒包装影响很小。发现HIV-1核衣壳蛋白7(NCp7)的N端碱性区域和碱性连接区域对于高效包装7SL RNA很重要。虽然Alu RNA源自7SL RNA并与7SL RNA共享Alu RNA结构域,但Alu RNA的包装效率比7SL RNA至少低50倍。因此,7SL RNA通过与病毒基因组RNA或引物tRNAlys,3不同的机制被选择性地包装进HIV-1病毒颗粒中。人胞苷脱氨酶载脂蛋白B mRNA编辑酶催化多肽样3(APOBEC3G)和细胞7SL RNA的病毒颗粒包装都定位到HIV-1 NC结构域的相同区域。