MicroRNA-dependent Localization of Targeted MRNAs to Mammalian P-bodies

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2005 Jun 7

PMID 15937477

Citations 537

Authors

Jidong Liu

Marco Antonio Valencia-Sanchez

Gregory J Hannon

Roy Parker

Affiliations

Soon will be listed here.

Abstract

Small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs) can silence target genes through several different effector mechanisms. Whereas siRNA-directed mRNA cleavage is increasingly understood, the mechanisms by which miRNAs repress protein synthesis are obscure. Recent studies have revealed the existence of specific cytoplasmic foci, referred to herein as processing bodies (P-bodies), which contain untranslated mRNAs and can serve as sites of mRNA degradation. Here we demonstrate that Argonaute proteins--the signature components of the RNA interference (RNAi) effector complex, RISC--localize to mammalian P-bodies. Moreover, reporter mRNAs that are targeted for translational repression by endogenous or exogenous miRNAs become concentrated in P-bodies in a miRNA-dependent manner. These results provide a link between miRNA function and mammalian P-bodies and suggest that translation repression by RISC delivers mRNAs to P-bodies, either as a cause or as a consequence of inhibiting protein synthesis.

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References

Sheth U, Parker R . Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science. 2003; 300(5620):805-8. PMC: 1876714. DOI: 10.1126/science.1082320. View

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

Newbury S, Woollard A . The 5'-3' exoribonuclease xrn-1 is essential for ventral epithelial enclosure during C. elegans embryogenesis. RNA. 2003; 10(1):59-65. PMC: 1370518. DOI: 10.1261/rna.2195504. View

Lewis B, Shih I, Jones-Rhoades M, Bartel D, Burge C . Prediction of mammalian microRNA targets. Cell. 2003; 115(7):787-98. DOI: 10.1016/s0092-8674(03)01018-3. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Janicki S, Tsukamoto T, Salghetti S, Tansey W, Sachidanandam R, Prasanth K . From silencing to gene expression: real-time analysis in single cells. Cell. 2004; 116(5):683-98. PMC: 4942132. DOI: 10.1016/s0092-8674(04)00171-0. View

Cougot N, Babajko S, Seraphin B . Cytoplasmic foci are sites of mRNA decay in human cells. J Cell Biol. 2004; 165(1):31-40. PMC: 2172085. DOI: 10.1083/jcb.200309008. View

Ma J, Ye K, Patel D . Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature. 2004; 429(6989):318-322. PMC: 4700412. DOI: 10.1038/nature02519. View

Souret F, Kastenmayer J, Green P . AtXRN4 degrades mRNA in Arabidopsis and its substrates include selected miRNA targets. Mol Cell. 2004; 15(2):173-83. DOI: 10.1016/j.molcel.2004.06.006. View

10.

Liu J, Carmell M, Rivas F, Marsden C, Thomson J, Song J . Argonaute2 is the catalytic engine of mammalian RNAi. Science. 2004; 305(5689):1437-41. DOI: 10.1126/science.1102513. View

11.

Meister G, Tuschl T . Mechanisms of gene silencing by double-stranded RNA. Nature. 2004; 431(7006):343-9. DOI: 10.1038/nature02873. View

12.

Ambros V . The functions of animal microRNAs. Nature. 2004; 431(7006):350-5. DOI: 10.1038/nature02871. View

13.

Lee R, Feinbaum R, Ambros V . The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75(5):843-54. DOI: 10.1016/0092-8674(93)90529-y. View

14.

Wightman B, Ha I, Ruvkun G . Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993; 75(5):855-62. DOI: 10.1016/0092-8674(93)90530-4. View

15.

Gazzani S, Lawrenson T, Woodward C, Headon D, Sablowski R . A link between mRNA turnover and RNA interference in Arabidopsis. Science. 2004; 306(5698):1046-8. DOI: 10.1126/science.1101092. View

16.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

17.

Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J . Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell. 2005; 120(5):623-34. DOI: 10.1016/j.cell.2004.12.038. View

18.

Orban T, Izaurralde E . Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome. RNA. 2005; 11(4):459-69. PMC: 1370735. DOI: 10.1261/rna.7231505. View

19.

Teixeira D, Sheth U, Valencia-Sanchez M, Brengues M, Parker R . Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA. 2005; 11(4):371-82. PMC: 1370727. DOI: 10.1261/rna.7258505. View

20.

Andrei M, Ingelfinger D, Heintzmann R, Achsel T, Rivera-Pomar R, Luhrmann R . A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. RNA. 2005; 11(5):717-27. PMC: 1370757. DOI: 10.1261/rna.2340405. View