Suppression of eukaryotic translation termination by selected RNAs

被引:20
作者
Carnes, J
Frolova, L
Zinnen, S
Drugeon, G
Phillippe, M
Justesen, J
Haenni, AL
Leinwand, L
Kisselev, LL
Yarus, M [1 ]
机构
[1] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
[2] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 117984, Russia
[3] Ribozyme Pharmaceut Inc, Boulder, CO 80301 USA
[4] Inst Jacques Monod, F-75251 Paris 05, France
[5] CNRS UPR 41, Dept Biol Genet Dev, F-35043 Rennes, France
[6] Aarhus Univ, Dept Mol & Struct Biol, DK-8000 Aarhus C, Denmark
关键词
aptamer; human; inhibitor; release factor; stop codon;
D O I
10.1017/S1355838200001242
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
Using selection-amplification, we have isolated RNAs with affinity for translation termination factors eRF1 and eRF1(.)eRF3 complex, Individual RNAs not only bind, but inhibit eRf1-mediated release of a model nascent chain from eukaryotic ribosomes, There is also significant but weaker inhibition of eRF1-stimulated eRF3 GTPase and eRF3 stimulation of eRF1 release activity, These latter selected RNAs therefore hinder eRF1(.)eRF3 interactions, Finally, four RNA inhibitors of release suppress a UAG stop codon in mammalian extracts dependent for termination on eRF1 from several metazoan species. These RNAs are therefore new specific inhibitors for the analysis of eukaryotic termination, and potentially a new class of omnipotent termination suppressors with possible therapeutic significance.
引用
收藏
页码:1468 / 1479
页数:12
相关论文
共 55 条
  • [1] Mutations in RNAs of both ribosomal subunits cause defects in translation termination
    Arkov, AL
    Freistroffer, DV
    Ehrenberg, M
    Murgola, EJ
    [J]. EMBO JOURNAL, 1998, 17 (05) : 1507 - 1514
  • [2] Placement of protein and RNA structures into a 5 Å-resolution map of the 50S ribosomal subunit
    Ban, N
    Nissen, P
    Hansen, J
    Capel, M
    Moore, PB
    Steitz, TA
    [J]. NATURE, 1999, 400 (6747) : 841 - 847
  • [3] BROWN CM, 1994, J BIOL CHEM, V269, P33164
  • [4] Polypeptide chain release factors
    Buckingham, RH
    Grentzmann, G
    Kisselev, L
    [J]. MOLECULAR MICROBIOLOGY, 1997, 24 (03) : 449 - 456
  • [5] CANTOR CR, 1979, TRANSFER RNA STRUCTU, P363
  • [6] Caskey C T, 1974, Methods Enzymol, V30, P293
  • [7] X-ray crystal structures of 70S ribosome functional complexes
    Cate, JH
    Yusupov, MM
    Yusupova, GZ
    Earnest, TN
    Noller, HF
    [J]. SCIENCE, 1999, 285 (5436) : 2095 - 2104
  • [8] Ciesiolka J, 1996, METHOD ENZYMOL, V267, P315
  • [9] USE OF TRANSFER-RNA SUPPRESSORS TO PROBE REGULATION OF ESCHERICHIA-COLI RELEASE FACTOR-II
    CURRAN, JF
    YARUS, M
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1988, 203 (01) : 75 - 83
  • [10] The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs
    Czaplinski, K
    Ruiz-Echevarria, MJ
    Paushkin, SV
    Han, X
    Weng, YM
    Perlick, HA
    Dietz, HC
    Ter-Avanesyan, MD
    Peltz, SW
    [J]. GENES & DEVELOPMENT, 1998, 12 (11) : 1665 - 1677