Ribozyme-mediated inhibition of HIV 1 suggests nucleolar trafficking of HIV-1 RNA

被引:94
作者
Michienzi, A
Cagnon, L
Bahner, I
Rossi, JJ [1 ]
机构
[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Grad Sch Biol Sci, Duarte, CA 91010 USA
关键词
D O I
10.1073/pnas.97.16.8955
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The HIV regulatory proteins Tat and Rev have a nucleolar localization property in human cells. However, no functional role has been attributed to this localization. Recently it has been demonstrated that expression of Rev induces nucleolar relocalization of some protein factors involved in Rev export. Because the function of Rev is to bind HIV RNA and facilitate transport of singly spliced and unspliced RNA to the cytoplasm, it is likely that the nucleolus plays a critical role in HIV-1 RNA export. As a test for trafficking of HIV-1 RNAs into the nucleolus, a hammerhead ribozyme that specifically cleaves HIV-1 RNA was inserted into the body of the U16 small nucleolar RNA, resulting in accumulation of the ribozyme within the nucleoli of human cells. HeLa CD4(+) and T cells expressing this nucleolar localized ribozyme exhibit dramatically suppressed HIV-1 replication. The results presented here suggest a trafficking of HIV-1 RNA through the nucleoli of human cells, thus posing a different paradigm for lentiviral RNA processing.
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页码:8955 / 8960
页数:6
相关论文
共 58 条
  • [1] REV IS NECESSARY FOR TRANSLATION BUT NOT CYTOPLASMIC ACCUMULATION OF HIV-1 VIF, VPR, AND ENV/VPU-2 RNAS
    ARRIGO, SJ
    CHEN, ISY
    [J]. GENES & DEVELOPMENT, 1991, 5 (05) : 808 - 819
  • [2] Nucleolar localization of early tRNA processing
    Bertrand, E
    Houser-Scott, F
    Kendall, A
    Singer, RH
    Engelke, DR
    [J]. GENES & DEVELOPMENT, 1998, 12 (16) : 2463 - 2468
  • [3] BOC SO, 1998, VIROLOGY, V244, P473
  • [4] NUCLEOLAR LOCALIZATION OF MYC TRANSCRIPTS
    BOND, VC
    WOLD, B
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (06) : 3221 - 3230
  • [5] The Rev protein is able to transport to the cytoplasm small nucleolar RNAs containing a Rev binding element
    Buonomo, SBC
    Michienzi, A
    De Angelis, FG
    Bozzoni, I
    [J]. RNA, 1999, 5 (08) : 993 - 1002
  • [6] In vivo identification of nuclear factors interacting with the conserved elements of box C/D small nucleolar RNAs
    Caffarelli, E
    Losito, M
    Giorgi, C
    Fatica, A
    Bozzoni, I
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (02) : 1023 - 1028
  • [7] SPECIFIC INTERACTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS REV PROTEIN WITH A STRUCTURED REGION IN THE ENV MESSENGER-RNA
    COCHRANE, AW
    CHEN, CH
    ROSEN, CA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (03) : 1198 - 1202
  • [8] SUBCELLULAR-LOCALIZATION OF THE HUMAN IMMUNODEFICIENCY VIRUS TRANS-ACTING ART GENE-PRODUCT
    CULLEN, BR
    HAUBER, J
    CAMPBELL, K
    SODROSKI, JG
    HASELTINE, WA
    ROSEN, CA
    [J]. JOURNAL OF VIROLOGY, 1988, 62 (07) : 2498 - 2501
  • [9] THE REV PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROMOTES POLYSOMAL ASSOCIATION AND TRANSLATION OF GAG/POL AND VPU/ENV MESSENGER-RNAS
    DAGOSTINO, DM
    FELBER, BK
    HARRISON, JE
    PAVLAKIS, GN
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (03) : 1375 - 1386
  • [10] INTRACELLULAR TRAFFICKING OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV PROTEIN - INVOLVEMENT OF CONTINUED RIBOSOMAL-RNA SYNTHESIS IN NUCLEAR RETENTION
    DAGOSTINO, DM
    CIMINALE, V
    PAVLAKIS, GN
    CHIECOBIANCHI, L
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 1995, 11 (09) : 1063 - 1071