Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation

被引：86

作者：

Ajamian, Lara ^{[1
,2
]}

Abrahamyan, Levon ^{[1
]}

Milev, Miroslav ^{[1
,2
]}

Ivanov, Pavel V. ^{[3
]}

Kulozik, Andreas E. ^{[3
]}

Gehring, Niels H. ^{[3
]}

Mouland, Andrew J. ^{[1
,2
]}

机构：

[1] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, RNA Trafficking Lab, HIV 1, Montreal, PQ H3T 1E2, Canada

[2] McGill Univ, Div Expt Med, Dept Med, Montreal, PQ H3A 2B4, Canada

[3] Heidelberg Univ, Univ Children Hosp, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany

来源：

RNA | 2008年 / 14卷 / 05期

关键词：

AIDS; HIV-1; UPF1; RNA stability;

D O I：

10.1261/rna.829208

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The HIV-1 ribonucleoprotein (RNP) contains the major structural protein, pr55 Gag, viral genomic RNA, as well as the host protein, Staufen1. In this report, we show that the nonsense-mediated decay (NMD) factor UPF1 is also a component of the HIV-1 RNP. We investigated the role of UPF1 in HIV-1-expressing cells. Depletion of UPF1 by siRNA resulted in a dramatic reduction in steady-state HIV-1 RNA and pr55 Gag. Pr55 Gag synthesis, but not the cognate genomic RNA, was efficiently rescued by expression of an siRNA-insensitive UPF1, demonstrating that UPF1 positively influences HIV-1 RNA translatability. Conversely, overexpression of UPF1 led to a dramatic up-regulation of HIV-1 expression at the RNA and protein synthesis levels. The effects of UPF1 on HIV-1 RNA stability were observed in the nucleus and cytoplasm and required ongoing translation. We also demonstrate that the effects exerted by UPF1 on HIV-1 expression were dependent on its ATPase activity, but were separable from its role in NMD and did not require interaction with UPF2.

引用

页码：914 / 927

页数：14

共 62 条

[1] The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila [J].