EVIDENCE THAT HIV-1 REV DIRECTLY PROMOTES THE NUCLEAR EXPORT OF UNSPLICED RNA

被引:222
作者
FISCHER, U
MEYER, S
TEUFEL, M
HECKEL, C
LUHRMANN, R
RAUTMANN, G
机构
[1] INST MOLEK BIOL & TUMORFORSCH,D-35037 MARBURG,GERMANY
[2] MARION MERRELL DOW RES INST,STRASBOURG RES CTR,F-67080 STRASBOURG,FRANCE
关键词
HIV-1; MESSENGER-RNA SPLICING; NUCLEAR RNA EXPORT; REV PROTEIN; XENOPUS LAEVIS OOCYTES;
D O I
10.1002/j.1460-2075.1994.tb06728.x
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 Rev trans-activator of human immmunodeficiency virus type 1 (HIV-1) is a protein that regulates the simultaneous appearance in the cytoplasm of both spliced and unspliced forms of viral mRNAs from the same viral transcripts by way of recognition of a target sequence termed the Rev-responsive element (RRE). Whether Rev acts directly on RNA export or by inhibition of splicing, or both, is still a matter of debate. We have addressed this issue in Xenopus laevis oocytes by microinjecting RNA molecules containing RRE along with purified recombinant Rev protein into the oocyte nuclei. Adenovirus pre-mRNA containing an RRE in the intron was spliced equally well in the absence and presence of Rev protein. Only in the presence of Rev was non-spliced pre-mRNA exported from the nucleus; more surprisingly, the excised intron lariat (containing RRE) was also exported. Furthermore, an RRE-containing mRNA molecule that lacked intron sequences was also efficiently exported from the nucleus in a Rev-dependent manner. Therefore our results demonstrate that Rev can act directly at the level of nuclear export, independent of any inhibitory effect that it may exert on the splicing of pre-mRNA. Finally, our finding that the Rev mutant M10, shown previously to be inactive in human lymphoid cells, was also unable to export RRE-containing RNA molecules from oocyte nuclei suggests that one or more cellular factors, evolutionarily conserved between humans and Xenopus, interact with Rev in both cell systems to promote nuclear RNA export.
引用
收藏
页码:4105 / 4112
页数:8
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