Inhibition of translational initiation by Let-7 microRNA in human cells

被引:1048
作者
Pillai, RS
Bhattacharyya, SN
Artus, CG
Zoller, T
Cougot, N
Basyuk, E
Bertrand, E
Filipowicz, W [1 ]
机构
[1] Friedrich Miescher Inst Biomed Res, CH-4002 Basel, Switzerland
[2] Inst Genet Mol Montpellier, F-34000 Montpellier, France
关键词
D O I
10.1126/science.1115079
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
MicroRNAs (miRNAs) are similar to 21-nucteotide-long RNA molecules regulating gene expression in multicellular eukaryotes. In metazoa, miRNAs act by imperfectly base-pairing with the 3' untranslated region of target messenger RNAs (mRNAs) and repressing protein accumulation by an unknown mechanism. We demonstrate that endogenous let-7 microribonucleoproteins (miRNPs) or the tethering of Argonaute (Ago) proteins to reporter mRNAs in human cells inhibit translation initiation. M(7)G-cap-independent translation is not subject to repression, suggesting that miRNPs interfere with recognition of the cap. Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression.
引用
收藏
页码:1573 / 1576
页数:4
相关论文
共 25 条
  • [1] Anderson P, 2002, J CELL SCI, V115, P3227
  • [2] A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies
    Andrei, MA
    Ingelfinger, D
    Heintzmann, R
    Achsel, T
    Rivera-Pomar, R
    Lührmann, R
    [J]. RNA, 2005, 11 (05) : 717 - 727
  • [3] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004)
    Bartel, David P.
    [J]. CELL, 2007, 131 (04) : 11 - 29
  • [4] bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila
    Brennecke, J
    Hipfner, DR
    Stark, A
    Russell, RB
    Cohen, SM
    [J]. CELL, 2003, 113 (01) : 25 - 36
  • [5] CHANG J, 2004, RNA BIOL, V1, P2
  • [6] A new paradigm for translational control:: Inhibition via 5′-3′ mRNA tethering by Bicoid and the eIF4E cognate 4EHP
    Cho, PF
    Poulin, F
    Cho-Park, YA
    Cho-Park, IB
    Chicoine, JD
    Lasko, P
    Sonenberg, N
    [J]. CELL, 2005, 121 (03) : 411 - 423
  • [7] Tethered-function analysis reveals that elF4E can recruit ribosomes independent of its binding to the cap structure
    De Gregorio, E
    Baron, J
    Preiss, T
    Hentze, MW
    [J]. RNA, 2001, 7 (01) : 106 - 113
  • [8] siRNAs can function as miRNAs
    Doench, JG
    Petersen, CP
    Sharp, PA
    [J]. GENES & DEVELOPMENT, 2003, 17 (04) : 438 - 442
  • [9] Molecular mechanisms of translational control
    Gebauer, F
    Hentze, MW
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (10) : 827 - 835
  • [10] Internal ribosome entry sites in eukaryotic mRNA molecules
    Hellen, CUT
    Sarnow, P
    [J]. GENES & DEVELOPMENT, 2001, 15 (13) : 1593 - 1612