Skip to main content Accessibility help
×
Home
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 1
  • Print publication year: 2007
  • Online publication date: August 2009

6 - Inhibition of translation initiation by a microRNA

from II - MicroRNA functions and RNAi-mediated pathways

Summary

Introduction

MicroRNAs (miRNAs) are small (∼22 nt) regulatory RNAs that are processed from stem-loop-forming precursor transcripts (Bartel, 2004; He and Hannon, 2004; Meister and Tuschl, 2004). In recent years, they have become the subject of intensive research, which quickly amassed a wealth of information on their biogenesis, function and significance for gene regulation. It also became apparent that miRNAs are an abundant class of gene regulators. The miRBase database (Release 7.1) lists 3424 miRNA sequence entries from various metazoa, plants and some viruses. Entries for intensely studied organisms number in the hundreds of distinct miRNA sequences, many of which exhibit phylogenetic conservation (Griffiths-Jones, 2004). Bioinformatic analyses predict that each miRNA will target multiple mRNAs (Lewis et al., 2003; Bartel, 2004; Lai, 2004; Brennecke et al., 2005; Krek et al., 2005), suggesting that, collectively, these novel gene regulators affect the expression of large portions of the cellular transcriptome. The biological significance of miRNAs is further corroborated by studies of individual examples, reporting their roles in diverse cellular and developmental pathways (see Brennecke et al., 2003; Johnston and Hobert, 2003; Xu et al., 2003; Chen et al., 2004; Zhao et al., 2005).

The miRNAs assemble into RNA–protein complexes, usually termed miRNP or RISC (for RNA-induced silencing complex). Different purification schemes have identified a number of resident proteins of miRNP/RISC complexes, with a member of the Argonaute (Ago) protein family consistently found in each preparation (Mourelatos et al., 2002; Dostie et al., 2003; Jin et al., 2004; Chendrimada et al., 2005; Meister et al., 2005).

Related content

Powered by UNSILO
References
Ambros, V. (2004). The functions of animal microRNAs. Nature, 431, 350–355.
Andrei, M. A., Ingelfinger, D., Heintzmann, R.et al. (2005). A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA, 11, 717–727.
Bagga, S., Bracht, J., Hunter, S.et al. (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell, 122, 553–563.
Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.
Bergamini, G., Preiss, T. and Hentze, M. W. (2000). Picornavirus IRESes and the poly(A) tail jointly promote cap-independent translation in a mammalian cell-free system. RNA, 6, 1781–190.
Brengues, M., Teixeira, D. and Parker, R. (2005). Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science, 310, 486–489.
Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B. and Cohen, S. M. (2003). Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113, 25–36.
Brennecke, J., Stark, A., Russell, R. B. and Cohen, S. M. (2005). Principles of microRNA-target recognition. Public Library of Science Biology, 3, e85.
Chen, C. Z., Li, L., Lodish, H. F. and Bartel, D. P. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science, 303, 83–86.
Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E.et al. (2005). TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature, 436, 740–774.
Chendrimada, T. P., Finn, K. J., Ji, X.et al. (2007). MicroRNA silencing through RISC recruitment of eIF6. Nature, 447, 823–829.
Cho, P. F., Poulin, F., Cho-Park, Y. A.et al. (2005). A new paradigm for translational control: inhibition via 5′-3′ mRNA tethering by Bicoid and the eIF4E cognate 4EHP. Cell, 121, 411–423.
Coller, J. and Parker, R. (2005). General translational repression by activators of mRNA decapping. Cell, 122, 875–886.
Cougot, N., Babajko, S. and Seraphin, B. (2004). Cytoplasmic foci are sites of mRNA decay in human cells. Journal of Cell Biology, 165, 31–40.
Cullen, B. R. (2004). Derivation and function of small interfering RNAs and microRNAs. Virus Res, 102, 3–9.
Doench, J. G. and Sharp, P. A. (2004). Specificity of microRNA target selection in translational repression. Genes & Development, 18, 504–511.
Doench, J. G., Petersen, C. P. and Sharp, P. A. (2003). siRNAs can function as miRNAs. Genes & Development, 17, 438–442.
Dostie, J., Mourelatos, Z., Yang, M., Sharma, A. and Dreyfuss, G. (2003). Numerous microRNPs in neuronal cells containing novel microRNAs. RNA, 9, 180–186.
Ferraiuolo, M. A., Basak, S., Dostie, J.et al. (2005). A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay. Journal of Cell Biology, 170, 913–924.
Gallie, D. R. (1991). The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. Genes & Development, 5, 2108–2116.
Gebauer, F. and Hentze, M. W. (2004). Molecular mechanisms of translational control. Nature Review of Molecular and Cell Biology, 5, 827–835.
Griffiths-Jones, S. (2004). The microRNA Registry. Nucleic Acids Research, 32, D109–111.
He, L. and Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature Review Genetics, 5, 522–531.
Hellen, C. U. and Sarnow, P. (2001). Internal ribosome entry sites in eukaryotic mRNA molecules. Genes & Development, 15, 1593–1612.
Humphreys, D. T., Westman, B. J., Martin, D. I. and Preiss, T. (2005). MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proceedings of the National Academy of Sciences USA, 102, 16 961–16 966.
Iizuka, N., Najita, L., Franzusoff, A. and Sarnow, P. (1994). Cap-dependent and cap-independent translation by internal initiation of mRNAs in cell extracts prepared from Saccharomyces cerevisiae. Molecular Cell Biology, 14, 7322–7330.
Jackson, R. J. (2000). Comparative view of initiation site selection mechanisms. In Translational Control of Gene Expression, Sonenberg, N. and Mathews, M. B. (eds.). Cold Spring Harbor, pp. 127–184.
Jakymiw, A., Lian, S., Eystathioy, T.et al. (2005). Disruption of GW bodies impairs mammalian RNA interference. Nature Cell Biology, 7, 1167–1174.
Jin, P., Zarnescu, D. C., Ceman, S.et al. (2004). Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nature Neuroscience, 7, 113–117.
Johnston, R. J. and Hobert, O. (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature, 426, 845–849.
Kahvejian, A., Svitkin, Y. V., Sukarieh, R., M'Boutchou, M. N. and Sonenberg, N. (2005). Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms. Genes & Development, 19, 104–113.
Kiriakidou, M., Tan, G. S., Lamprinaki, S.et al. (2007). An mRNA m7G Cap binding-like motif within human Ago2 represses translation. Cell, 129, 1141–1151.
Krek, A., Grun, D., Poy, M. N.et al. (2005). Combinatorial microRNA target predictions. Nature Genetics, 37, 495–500.
Ladomery, M., Wade, E. and Sommerville, J. (1997). Xp54, the Xenopus homologue of human RNA helicase p54, is an integral component of stored mRNP particles in oocytes. Nucleic Acids Research, 25, 965–973.
Lai, E. C. (2004). Predicting and validating microRNA targets. Genome Biology, 5, 115.
Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P. and Burge, C. B. (2003). Prediction of mammalian microRNA targets. Cell, 115, 787–798.
Liu, J., Valencia-Sanchez, M. A., Hannon, G. J. and Parker, R. (2005). MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biology, 7, 719–723.
Marx, J. (2005). Molecular biology. P-bodies mark the spot for controlling protein production. Science, 310, 764–765.
Meister, G. and Tuschl, T. (2004). Mechanisms of gene silencing by double-stranded RNA. Nature, 431, 343–349.
Meister, G., Landthaler, M., Patkaniowska, A.et al. (2004). Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Molecular Cell, 15, 185–197.
Meister, G., Landthaler, M., Peters, L.et al. (2005). Identification of novel argonaute-associated proteins. Current Biology, 15, 2149–2155.
Minshall, N. and Standart, N. (2004). The active form of Xp54 RNA helicase in translational repression is an RNA-mediated oligomer. Nucleic Acids Research, 32, 1325–1334.
Mourelatos, Z., Dostie, J., Paushkin, S.et al. (2002). miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes & Development, 16, 720–728.
Nakamura, A., Amikura, R., Hanyu, K. and Kobayashi, S. (2001). Me31B silences translation of oocyte-localizing RNAs through the formation of cytoplasmic RNP complex during Drosophila oogenesis. Development, 128, 3233–3242.
Nakamura, A., Sato, K. and Hanyu-Nakamura, K. (2004). Drosophila cup is an eIF4E binding protein that associates with Bruno and regulates oskar mRNA translation in oogenesis. Developmental Cell, 6, 69–78.
Nelson, M. R., Leidal, A. M. and Smibert, C. A. (2004). Drosophila Cup is an eIF4E-binding protein that functions in Smaug-mediated translational repression. European Molecular Biology Organization Journal, 23, 150–159.
Nottrott, S., Simard, M. J. and Richter, J. D. (2006). Human let-7a miRNA blocks protein on actively translating polyribosomes. Nature Structural & Molecular Biology, 13, 1108–1114.
Olsen, P. H. and Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology, 216, 671–680.
Ostareck, D. H., Ostareck-Lederer, A., Shatsky, I. N. and Hentze, M. W. (2001). Lipoxygenase mRNA silencing in erythroid differentiation: The 3′ UTR regulatory complex controls 60 S ribosomal subunit joining. Cell, 104, 281–290.
Pasquinelli, A. E. and Ruvkun, G. (2002). Control of developmental timing by microRNAs and their targets. Annual Review of Cell and Developmental Biology, 18, 495–513.
Pestova, T. V. and Hellen, C. U. (2003). Translation elongation after assembly of ribosomes on the Cricket paralysis virus internal ribosomal entry site without initiation factors or initiator tRNA. Genes & Development, 17, 181–186.
Petersen, C. P., Bordeleau, M., Pelletier, J. and Sharp, P. A. (2006). Short RNAs Repress Translation after Initiation in Mammalian Cells. Molecular Cell, 21, 533–542.
Pillai, R. S., Artus, C. G. and Filipowicz, W. (2004). Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. RNA, 10, 1518–1525.
Pillai, R. S., Bhattacharyya, S. N., Artus, C. G.et al. (2005). Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science, 309, 1573–1576.
Poyry, T. A., Kaminski, A. and Jackson, R. J. (2004). What determines whether mammalian ribosomes resume scanning after translation of a short upstream open reading frame? Genes & Development, 18, 62–75.
Preiss, T. and Hentze, M. W. (1998). Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast. Nature, 392, 516–520.
Preiss, T. and Hentze, M. W. (2003). Starting the protein synthesis machine: eukaryotic translation initiation. Bioessays, 25, 1201–1211.
Richter, J. D. and Sonenberg, N. (2005). Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature, 433, 477–480.
Sachs, A. (2000). Physical and functional interactions between the mRNA cap structure and the poly(A) tail. In Translational Control of Gene Expression, Sonenberg, N. and Mathews, M. B. (eds.) Cold Spring Harbor, pp. 447–465.
Seggerson, K., Tang, L. and Moss, E. G. (2002). Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Developmental Biology, 243, 215–225.
Sen, G. L. and Blau, H. M. (2005). Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nature Cell Biology, 7, 633–636.
Sheth, U. and Parker, R. (2003). Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science, 300, 805–808.
Sonenberg, N. and Dever, T. E. (2003). Eukaryotic translation initiation factors and regulators. Current Opinion in Structural Biology, 13, 56–63.
Svitkin, Y. V., Imataka, H., Khaleghpour, K.et al. (2001). Poly(A)-binding protein interaction with elF4G stimulates picornavirus IRES-dependent translation. RNA, 7, 1743–1752.
Teixeira, D., Sheth, U., Valencia-Sanchez, M. A., Brengues, M. and Parker, R. (2005). Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA, 11, 371–382.
Thermann, R. and Hentzel, M. W. (2007). Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature, 447, 875–979.
Wang, B., Love, T. M., Call, M. E., Doench, J. G. and Novina, C. D. (2006). Recapitulation of short RNA-directed translational gene silencing in vitro. Molecular Cell, 22, 553–560.
Wilczynska, A., Aigueperse, C., Kress, M., Dautry, F. and Weil, D. (2005). The translational regulator CPEB1 provides a link between dcp1 bodies and stress granules. Journal of Cell Science, 118, 981–992.
Wilhelm, J. E., Hilton, M., Amos, Q. and Henzel, W. J. (2003). Cup is an eIF4E binding protein required for both the translational repression of oskar and the recruitment of Barentsz. Journal of Cell Biology, 163, 1197–1204.
Xu, P., Vernooy, S. Y., Guo, M. and Hay, B. A. (2003). The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Current Biology, 13, 790–795.
Zappavigna, V., Piccioni, F., Villaescusa, J. C. and Verrotti, A. C. (2004). Cup is a nucleocytoplasmic shuttling protein that interacts with the eukaryotic translation initiation factor 4E to modulate Drosophila ovary development. Proceedings of the National Academy of Sciences USA, 101, 14 800–14 805.
Zeng, Y. and Cullen, B. R. (2003). Sequence requirements for micro RNA processing and function in human cells. RNA, 9, 112–123.
Zeng, Y., Wagner, E. J. and Cullen, B. R. (2002). Both natural and designed microRNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular Cell, 9, 1327–1333.
Zhao, Y., Samal, E. and Srivastava, D. (2005). Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature, 436, 214–220.