MRNA Targeting to Endoplasmic Reticulum Precedes Ago Protein Interaction and MicroRNA (miRNA)-mediated Translation Repression in Mammalian Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2015 Aug 26

PMID 26304123

Citations 34

Authors

Bahnisikha Barman

Suvendra N Bhattacharyya

Affiliations

Soon will be listed here.

Abstract

MicroRNA (miRNA) binds to the 3'-UTR of its target mRNAs to repress protein synthesis. Extensive research was done to understand the mechanism of miRNA-mediated repression in animal cells. Considering the progress in understanding the mechanism, information about the subcellular sites of miRNA-mediated repression is surprisingly limited. In this study, using an inducible expression system for an miRNA target message, we have delineated how a target mRNA passes through polysome association and Ago2 interaction steps on rough endoplasmic reticulum (ER) before the miRNA-mediated repression sets in. From this study, de novo formed target mRNA localization to the ER-bound polysomes manifested as the earliest event, which is followed by Ago2 micro-ribonucleoprotein binding, and translation repression of target message. Compartmentalization of this process to rough ER membrane ensures enrichment of miRNA-targeted messages and micro-ribonucleoprotein components on ER upon reaching a steady state.

Citing Articles

The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).

Kozlov D, Rodimova S, Kuznetsova D Sovrem Tekhnologii Med. 2025; 15(5):54-79.

PMID: 39967915 PMC: 11832066. DOI: 10.17691/stm2023.15.5.06.

StaufenC facilitates utilization of the ERAD pathway to transport dsRNA through the endoplasmic reticulum to the cytosol.

Koo J, Palli S Proc Natl Acad Sci U S A. 2024; 121(26):e2322927121.

PMID: 38885386 PMC: 11214074. DOI: 10.1073/pnas.2322927121.

Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action.

Lin M, Kuo W, Chen S, Hsu J, Lu L, Wang C EMBO Rep. 2024; 25(5):2441-2478.

PMID: 38649663 PMC: 11094075. DOI: 10.1038/s44319-024-00132-7.

Direct observation of cytoskeleton-dependent trafficking of miRNA visualized by the introduction of pre-miRNA.

Ishikawa T, Sugawara K, Zhang J, Funatsu T, Okabe K iScience. 2024; 27(2):108811.

PMID: 38303695 PMC: 10831896. DOI: 10.1016/j.isci.2024.108811.

ER membrane contact sites: key platforms for biogenesis of RNA-containing extracellular vesicles.

Barman B, Dawson T, Weaver A Contact (Thousand Oaks). 2023; 5.

PMID: 37008559 PMC: 10065479. DOI: 10.1177/25152564221121444.

References

Stalder L, Heusermann W, Sokol L, Trojer D, Wirz J, Hean J . The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing. EMBO J. 2013; 32(8):1115-27. PMC: 3630355. DOI: 10.1038/emboj.2013.52. View

Li S, Liu L, Zhuang X, Yu Y, Liu X, Cui X . MicroRNAs inhibit the translation of target mRNAs on the endoplasmic reticulum in Arabidopsis. Cell. 2013; 153(3):562-74. PMC: 3694718. DOI: 10.1016/j.cell.2013.04.005. View

Mazumder A, Bose M, Chakraborty A, Chakrabarti S, Bhattacharyya S . A transient reversal of miRNA-mediated repression controls macrophage activation. EMBO Rep. 2013; 14(11):1008-16. PMC: 3851954. DOI: 10.1038/embor.2013.149. View

Jagannathan S, Reid D, Cox A, Nicchitta C . De novo translation initiation on membrane-bound ribosomes as a mechanism for localization of cytosolic protein mRNAs to the endoplasmic reticulum. RNA. 2014; 20(10):1489-98. PMC: 4174431. DOI: 10.1261/rna.045526.114. View

Ghosh S, Bose M, Ray A, Bhattacharyya S . Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA in growth-retarded mammalian cells. Mol Biol Cell. 2015; 26(6):1072-83. PMC: 4357507. DOI: 10.1091/mbc.E14-11-1521. View

Lerner R, Seiser R, Zheng T, Lager P, Reedy M, Keene J . Partitioning and translation of mRNAs encoding soluble proteins on membrane-bound ribosomes. RNA. 2003; 9(9):1123-37. PMC: 1370476. DOI: 10.1261/rna.5610403. View

Schenkman J, Cinti D . Preparation of microsomes with calcium. Methods Enzymol. 1978; 52:83-9. DOI: 10.1016/s0076-6879(78)52008-9. View

Fujiki Y, Hubbard A, Fowler S, Lazarow P . Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum. J Cell Biol. 1982; 93(1):97-102. PMC: 2112113. DOI: 10.1083/jcb.93.1.97. View

Wong W, Brostrom M, Kuznetsov G, Brostrom C . Inhibition of protein synthesis and early protein processing by thapsigargin in cultured cells. Biochem J. 1993; 289 ( Pt 1):71-9. PMC: 1132132. DOI: 10.1042/bj2890071. View

10.

Hamilton R, Moorehouse A, Lear S, Wong J, Erickson S . A rapid calcium precipitation method of recovering large amounts of highly pure hepatocyte rough endoplasmic reticulum. J Lipid Res. 1999; 40(6):1140-7. View

11.

Liu J, Valencia-Sanchez M, Hannon G, Parker R . MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005; 7(7):719-23. PMC: 1855297. DOI: 10.1038/ncb1274. View

12.

Pillai R, Bhattacharyya S, Artus C, Zoller T, Cougot N, Basyuk E . Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science. 2005; 309(5740):1573-6. DOI: 10.1126/science.1115079. View

13.

Bhattacharyya S, Habermacher R, Martine U, Closs E, Filipowicz W . Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell. 2006; 125(6):1111-24. DOI: 10.1016/j.cell.2006.04.031. View

14.

Maroney P, Yu Y, Fisher J, Nilsen T . Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat Struct Mol Biol. 2006; 13(12):1102-7. DOI: 10.1038/nsmb1174. View

15.

Nottrott S, Simard M, Richter J . Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol. 2006; 13(12):1108-14. DOI: 10.1038/nsmb1173. View

16.

Mathonnet G, Fabian M, Svitkin Y, Parsyan A, Huck L, Murata T . MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science. 2007; 317(5845):1764-7. DOI: 10.1126/science.1146067. View

17.

Hutvagner G, Simard M . Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol. 2007; 9(1):22-32. DOI: 10.1038/nrm2321. View

18.

Pyhtila B, Zheng T, Lager P, Keene J, Reedy M, Nicchitta C . Signal sequence- and translation-independent mRNA localization to the endoplasmic reticulum. RNA. 2008; 14(3):445-53. PMC: 2248262. DOI: 10.1261/rna.721108. View

19.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

20.

Gibbings D, Ciaudo C, Erhardt M, Voinnet O . Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol. 2009; 11(9):1143-9. DOI: 10.1038/ncb1929. View