Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis

RNA
Ramesh S PillaiWitold Filipowicz

Abstract

MicroRNAs (miRNAs) are approximately 21-nt-long RNAs involved in regulating development, differentiation, and other processes in eukaryotes. In metazoa, nearly all miRNAs control gene expression by imperfectly base-pairing with the 3'-untranslated region (3'-UTR) of target mRNAs and repressing protein synthesis by an unknown mechanism. It is also unknown whether miRNA-mRNA duplexes containing mismatches and bulges provide specific features that are recognized by factors mediating the repression. miRNAs form part of ribonucleoprotein complexes, miRNPs, that contain Argonaute (Ago) and other proteins. Here we demonstrate that effects of miRNAs on translation can be mimicked in human HeLa cells by the miRNA-independent tethering of Ago proteins to the 3'-UTR of a reporter mRNA. Inhibition of protein synthesis occurred without a change in the reporter mRNA level and was dependent on the number, but not the position, of the hairpins tethering hAgo2 to the 3'-UTR. These findings indicate that a primary function of miRNAs is to guide their associated proteins to the mRNA.

References

Mar 17, 2001·Nature Reviews. Genetics·S M HammondG J Hannon
Mar 27, 2002·Genes & Development·Zissimos MourelatosGideon Dreyfuss
Aug 3, 2002·Science·György Hutvágner, Phillip D Zamore
Sep 17, 2002·Cell·Javier MartinezThomas Tuschl
Oct 9, 2002·Genes & Development·Amy A CaudyScott M Hammond
Oct 9, 2002·Genes & Development·Akira IshizukaHaruhiko Siomi
Feb 26, 2003·Genes & Development·John G DoenchPhillip A Sharp
Apr 26, 2003·Trends in Biochemical Sciences·Ahmet M Denli, Gregory J Hannon
Apr 30, 2003·Molecular Cell·Niels H GehringAndreas E Kulozik
Aug 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yan ZengBryan R Cullen
Sep 4, 2003·Genome Biology·Julius Brennecke, Stephen M Cohen
Sep 26, 2003·Nature·Amy A CaudyRonald H A Plasterk
Feb 19, 2004·RNA·Peter T NelsonZissimos Mourelatos
Mar 12, 2004·Genes & Development·John G Doench, Phillip A Sharp
Apr 24, 2004·Genes & Development·Javier Martinez, Thomas Tuschl
May 8, 2004·Genes & Development·Marianthi KiriakidouArtemis Hatzigeorgiou
Jul 3, 2004·Genes & Development·Katsutomo OkamuraMikiko C Siomi

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Citations

Nov 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·David T HumphreysThomas Preiss
May 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·J Robin LytleJoan A Steitz
Oct 24, 2006·Journal of Biomedicine & Biotechnology·Dominique L OuelletPatrick Provost
Jun 25, 2009·Journal of Biomedicine & Biotechnology·Christian BarbatoAndrea Masotti
May 1, 2012·Journal of Signal Transduction·Rebecca Elston, Gareth J Inman
Sep 3, 2014·International Journal of Genomics·Ayla Valinezhad OrangMina Kazemzadeh-Bavili
Feb 1, 2012·Biomolecular Concepts·Victoria JamesTyson V Sharp
Aug 1, 2008·Nutrition Reviews·Cindy D Davis, Sharon A Ross
Jan 31, 2013·Journal of Molecular Cell Biology·Adam P CarrollMurray J Cairns
Nov 15, 2005·Nature Cell Biology·Jidong LiuGregory J Hannon
Jul 4, 2006·Genes & Development·Isabelle Behm-AnsmantElisa Izaurralde
Sep 15, 2006·Nucleic Acids Research·Daniela SchmitterWitold Filipowicz
Jan 15, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alla MusiyenkoSailen Barik
Jul 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sven DiederichsDaniel A Haber
Jul 8, 2008·Nucleic Acids Research·Kirsi PaukkuJukka Y A Lehtonen
Aug 15, 2008·Molecular Biology of the Cell·Karin Lykke-AndersenMagdalena Zernicka-Goetz
Nov 26, 2008·RNA·Ana EulalioElisa Izaurralde
Jan 29, 2009·Genes & Development·Hong SuXiaozhong Wang
Feb 28, 2009·Circulation Research·Yajaira Suárez, William C Sessa
Aug 27, 2009·BMC Research Notes·Yukinobu HayashidaTsutomu Kurokawa
Oct 17, 2009·International Journal of Plant Genomics·Turgay UnverHikmet Budak
Oct 20, 2009·Nature Structural & Molecular Biology·Chyi-Ying A ChenAnn-Bin Shyu
Jan 12, 2010·Nature Structural & Molecular Biology·Sergej DjuranovicRachel Green
Jan 13, 2010·Molecular and Cellular Biology·Xianghua PiaoJoel G Belasco
Feb 2, 2010·European Heart Journal·Gianluigi CondorelliGerald W Dorn
May 13, 2010·Silence·Shuo Gu, Mark A Kay
Nov 13, 2010·Nucleic Acids Research·Sabine RüdelGunter Meister
Dec 7, 2010·Nucleic Acids Research·Bing YaoEdward K L Chan
Dec 25, 2010·The Plant Cell·Allison Mallory, Hervé Vaucheret
Jul 15, 2011·Clinical and Experimental Gastroenterology·Claire M PayneHarris Bernstein
Feb 15, 2012·Advances in Nutrition·Sharon A Ross, Cindy D Davis
Jun 22, 2012·PLoS Biology·Thomas SweetJeff Coller
Sep 29, 2012·Genes & Development·Valérie HilgersMichael Levine
Nov 6, 2012·Nucleic Acids Research·Inga LoedigeWitold Filipowicz
Jan 19, 2013·The Journal of Biological Chemistry·Junho K HurRachel Green

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