期刊
ONCOGENE
卷 19, 期 32, 页码 3570-3575出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1203676
关键词
nuclear export; RNA helicase A; Sam68; Tap; RRE; CTE
资金
- NIGMS NIH HHS [GM56089] Funding Source: Medline
Unlike cellular mRNA, retroviral mRNA bypasses the tight coupling of the splicing and nuclear export steps to allow the export of intron-containing viral RNA transcripts to the cytoplasm. Two distinct nuclear export pathways for retroviral mRNA have been described: a CRM-1 dependent pathway mediated by the HIV-1 Rev protein and the Rev Response Element (RRE), and a CRM-1 independent pathway mediated by the Constitutive Transport Element (CTE) of type D retroviruses. Two CTE-binding proteins, RNA helicase A (RHA) and Tap, have been implicated in the nuclear export of CTE-containing RNA. Recently, we reported that expression of RRE-containing RNA could also be mediated by a cellular protein, Sam68, independently of Rev. Here we report evidence that Sam68, RHA and Tap cooperate in the nuclear export of both CTE- and RRE-containing RNA. RHA binds to Sam68 and to Tap both in vivo and in vitro. Over-expression of Sam68 activates both RRE-and CTE-regulated reporter gene expression in human cells and in quail cells in the presence of human lap. This activation was competitively inhibited by the nuclear transport domain (NTD) of RHA and a transdominant negative mutant of Tap. Conversely, the activation of CTE by Tap in quail cells was inhibited by a transdominant mutant of Sam68 and NTD. We propose that both HIV and type D retroviruses may access the same constitutive RNA nuclear export path tray involving RHA, Tap and Sam68, even though HIV also utilizes the Rev protein for more efficient nuclear export, it is likely that this constitutive export pathway is also used by cellular mRNA, but at a different interface with the splicing process.
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