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.
Keywords: cis-element, HIV-1, mRNA, Nef, translation.
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