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Current HIV Research
ISSN (Print): 1570-162X
ISSN (Online): 1873-4251
DOI: 10.2174/1570162X12666140701092331

Identification of Essential cis Element in 5'UTR of Nef mRNA for Nef Translation

Author(s): Minami Yamamoto, Keisuke Harada, Shozo Shoji, Shogo Misumi and Nobutoki Takamune
Pages 213-219 (7)
Nef is one of the accessory proteins of the human immunodeficiency virus type 1 (HIV-1). Nef is translated from multiple-spliced mRNAs transcribed from the viral genome, whose mRNAs have a relatively long 5' untranslated region (5'UTR). Here, we identified a cis element in the 5'UTR of Nef mRNA essential for efficient Nef translation, which was named the Nef-translation essential region (NER). Mutants with a deleted NER in the 5'UTR of the HIV-1 NL4-3 strain showed an almost undetectable Nef expression owing to a low Nef translation efficiency. The NER of the NL4-3 strain was predicted to form putative stem loops. Although the 5'UTR showed significant but relatively low internal ribosome entry site (IRES) activity, the mechanism of 5’cap-dependent translation mainly contributed to the Nef translation from its Nef mRNA. Altogether, it was clarified that not only the 5' cap but also the NER in the 5'UTR is an essential cis element for efficient Nef translation, which is not a typical 5'-cap-dependent mechanism, and that there must be an as yet unknown mechanism using the NER for efficient Nef translation.
Graphical Abstract:
cis-element, HIV-1, mRNA, Nef, translation.
Department of Pharmaceutical Biochemistry, Faculty of Life Sciences, Kumamoto University, 5-1 Oe- Honmachi, Chuo-ku, Kumamoto 862-0973, Japan.