translation agency

HIV-1 rev as a model nuclear RNA export factor.
Cullen BR; Howard Hughes Medical Institute, Duke University Medical
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:171. Unique

The HIV-1 Rev protein is the best understood protein involved in the nuclear export of specific target RNA species. Rev function requires two domains. The first is a basic domain that mediates 1) nuclear import of Rev 2) binding of Rev to its RNA sequence, the RRE, and 3) multimerization of Rev on the target RNA. A second critical domain, termed the Rev activation domain, is an [approx.] 10 amino acid leucine rich sequence that is critical for Rev function but dispensable for specific RNA binding. The activation domain has been shown to specifically bind a cellular, nucleoporin-like co-factor termed Rab or hRIP and also functions as an autonomous protein nuclear export signal (NES). Mutational analysis suggests that these three activities fully co-segregate, i.e. that the role of the Rev activation domain is to bind Rab which in turn induces the nuclear export of Rev and, hence, bound target RNA species. Functional domains equivalent to the Rev activation domain have recently been identified in TFIIIA which is believed to function in the nuclear export of 5S rRna and in PKI, which mediates the nuclear export of a cellular protein target. The PKI NES also binds Rab specifically and can, like the TFIIIA NES, fully substitute for the Rev activation domain in chimeric proteins. Therefore, it is clear that the Rev nuclear export pathway is used by multiple cellular factors and does not represent a dedicated RNA export pathway.

Biological Transport Cell Nucleus/*METABOLISM Chimeric Proteins/METABOLISM Gene Products, rev/GENETICS/*METABOLISM HIV-1/*METABOLISM RNA, Ribosomal, 5S/METABOLISM ABSTRACT