7SL RNA mediates virion packaging of the antiviral cytidine deaminase APOBEC3G.
Cytidine deaminase APOBEC3G (A3G) has broad antiviral activity against diverse retroviruses and/or retrotransposons, and its antiviral functions are believed to rely on its encapsidation into virions in an RNA-dependent fashion. However, the cofactors of A3G virion packaging have not yet been identified. We demonstrate here that A3G selectively interacts with certain polymerase III (Pol III)-derived RNAs, including Y3 and 7SL RNAs. Among A3G-binding Pol III-derived RNAs, 7SL RNA was preferentially packaged into human immunodeficiency virus type 1 (HIV-1) particles. Efficient packaging of 7SL RNA, as well as A3G, was mediated by the RNA-binding nucleocapsid domain of HIV-1 Gag. A3G mutants that had reduced 7SL RNA binding but maintained wild-type levels of mRNA and tRNA binding were packaged poorly and had impaired antiviral activity. Reducing 7SL RNA packaging by overexpression of SRP19 proteins inhibited 7SL RNA and A3G virion packaging and impaired its antiviral function. Thus, 7SL RNA that is encapsidated into diverse retroviruses is a key cofactor of the antiviral A3G. This selective interaction of A3G with certain Pol III-derived RNAs raises the question of whether A3G and its cofactors may have as-yet-unidentified cellular functions.
Wang
Tao
T
Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Tian
Chunjuan
C
Zhang
Wenyan
W
Luo
Kun
K
Sarkis
Phuong Thi Nguyen
PT
Yu
Lillian
L
Liu
Bindong
B
Yu
Yunkai
Y
Yu
Xiao-Fang
XF
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009154:Mutation; D020733:RNA, Small Cytoplasmic / Q000502:physiology*; D018271:Signal Recognition Particle / Q000502:physiology*; D019065:Virus Assembly / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
C115990:7SL RNA; D020733:RNA, Small Cytoplasmic; D018271:Signal Recognition Particle; D054301:gag Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase