Activation of a MicroRNA Response in Trans Reveals a New Role for Poly(A) in Translational Repression

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2011 Mar 10

PMID 21385827

Citations 19

Authors

Emiliano P Ricci

Taran Limousin

Ricardo Soto-Rifo

Rachel Allison

Tuija Poyry

Didier Decimo

Richard J Jackson

Theophile Ohlmann

Affiliations

Soon will be listed here.

Abstract

Here, we report that the untreated rabbit reticulocyte lysate contains over 300 different endogenous microRNAs together with the major components of the RNA-induced silencing complex and thus can be used as a model in vitro system to study the effects of microRNAs on gene expression. By using this system, we were able to show that microRNA hybridization to its target resulted in a very rapid and strong inhibition of expression that was exerted exclusively at the level of translation initiation with no involvement of transcript degradation or deadenylation. Moreover, we demonstrate that the magnitude of microRNA-induced repression can only be recapitulated in the context of a competitive translating environment. By using a wide spectrum of competitor cellular and viral RNAs, we could further show that competition was not exerted at the level of general components of the translational machinery, but relied exclusively on the presence of the poly(A) tail with virtually no involvement of the cap structure.

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References

Dore L, Amigo J, Dos Santos C, Zhang Z, Gai X, Tobias J . A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A. 2008; 105(9):3333-8. PMC: 2265118. DOI: 10.1073/pnas.0712312105. View

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

Thermann R, Hentze M . Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature. 2007; 447(7146):875-8. DOI: 10.1038/nature05878. View

Masaki S, Ohtsuka R, Abe Y, Muta K, Umemura T . Expression patterns of microRNAs 155 and 451 during normal human erythropoiesis. Biochem Biophys Res Commun. 2007; 364(3):509-14. DOI: 10.1016/j.bbrc.2007.10.077. View

Baek D, Villen J, Shin C, Camargo F, Gygi S, Bartel D . The impact of microRNAs on protein output. Nature. 2008; 455(7209):64-71. PMC: 2745094. DOI: 10.1038/nature07242. View

Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R . Fast and effective prediction of microRNA/target duplexes. RNA. 2004; 10(10):1507-17. PMC: 1370637. DOI: 10.1261/rna.5248604. View

Hunt S, Jackson R . Polypyrimidine-tract binding protein (PTB) is necessary, but not sufficient, for efficient internal initiation of translation of human rhinovirus-2 RNA. RNA. 1999; 5(3):344-59. PMC: 1369764. DOI: 10.1017/s1355838299981414. View

Soto Rifo R, Ricci E, Decimo D, Moncorge O, Ohlmann T . Back to basics: the untreated rabbit reticulocyte lysate as a competitive system to recapitulate cap/poly(A) synergy and the selective advantage of IRES-driven translation. Nucleic Acids Res. 2007; 35(18):e121. PMC: 2094066. DOI: 10.1093/nar/gkm682. View

Hon L, Zhang Z . The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression. Genome Biol. 2007; 8(8):R166. PMC: 2374997. DOI: 10.1186/gb-2007-8-8-r166. View

10.

Maroney P, Chamnongpol S, Souret F, Nilsen T . A rapid, quantitative assay for direct detection of microRNAs and other small RNAs using splinted ligation. RNA. 2007; 13(6):930-6. PMC: 1869037. DOI: 10.1261/rna.518107. View

11.

Chu C, Rana T . Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54. PLoS Biol. 2006; 4(7):e210. PMC: 1475773. DOI: 10.1371/journal.pbio.0040210. View

12.

Song J, Smith S, Hannon G, Joshua-Tor L . Crystal structure of Argonaute and its implications for RISC slicer activity. Science. 2004; 305(5689):1434-7. DOI: 10.1126/science.1102514. View

13.

Wang B, Love T, Call M, Doench J, Novina C . Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell. 2006; 22(4):553-60. DOI: 10.1016/j.molcel.2006.03.034. View

14.

Pase L, Layton J, Kloosterman W, Carradice D, Waterhouse P, Lieschke G . miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2. Blood. 2008; 113(8):1794-804. PMC: 2647672. DOI: 10.1182/blood-2008-05-155812. View

15.

Pauley K, Eystathioy T, Jakymiw A, Hamel J, Fritzler M, Chan E . Formation of GW bodies is a consequence of microRNA genesis. EMBO Rep. 2006; 7(9):904-10. PMC: 1559661. DOI: 10.1038/sj.embor.7400783. View

16.

Doench J, Petersen C, Sharp P . siRNAs can function as miRNAs. Genes Dev. 2003; 17(4):438-42. PMC: 195999. DOI: 10.1101/gad.1064703. View

17.

Piao X, Zhang X, Wu L, Belasco J . CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells. Mol Cell Biol. 2010; 30(6):1486-94. PMC: 2832495. DOI: 10.1128/MCB.01481-09. View

18.

Borman A, Michel Y, Kean K . Biochemical characterisation of cap-poly(A) synergy in rabbit reticulocyte lysates: the eIF4G-PABP interaction increases the functional affinity of eIF4E for the capped mRNA 5'-end. Nucleic Acids Res. 2000; 28(21):4068-75. PMC: 113128. DOI: 10.1093/nar/28.21.4068. View

19.

Meister G, Landthaler M, Dorsett Y, Tuschl T . Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA. 2004; 10(3):544-50. PMC: 1370948. DOI: 10.1261/rna.5235104. View

20.

Cheloufi S, Dos Santos C, Chong M, Hannon G . A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature. 2010; 465(7298):584-9. PMC: 2995450. DOI: 10.1038/nature09092. View