mRNA targeting to endoplasmic reticulum precedes ago protein interaction and microRNA (miRNA)-mediated translation repression in mammalian cells
Open accessAbstract
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.
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miRISC and target mRNA localize in multiple subcellular compartments including rough endoplasmic reticulum, P-bodies, stress granules, trans-Golgi network, early/late endosomes, multivesicular bodies, lysosomes, mitochondria, and the nucleus.
“miRISC and target mRNA have been observed to localize in multiple subcellular compartments including rough endoplasmic reticulum (rER) (70), processing (P)-bodies (71), stress granules (SG) (72), the trans-Golgi network (TGN), early/late endosomes (73), multivesicular bodies (MVB) (74), lysosomes (74), mitochondria (75, 76), and the nucleus (66, 77) (Figure 2).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [70]
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- Authors
- Barman, B., & Bhattacharyya, S. N.
- Affiliations
- Indian Institute of Chemical Biology (IN)
- Corresponding author
- Bhattacharyya, Suvendra N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 290
- Issue
- 41
- Pages
- 24650-24656
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4598978
- OpenAlex
- W1933173778
- Cited by
- 86
- References
- 23
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 15 · 2021: 12 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 5
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (WT084324MF)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- microRNA, mRNA localization, rough endoplasmic reticulum, polysome association, Argonaute 2, 3' untranslated region, subcellular targeting
- MeSH terms
- RAW 264.7 Cells, Animals, Endoplasmic Reticulum, Humans, Intracellular Membranes, Polyribosomes, Protein Binding, RNA, Messenger, Protein Biosynthesis, Protein Transport, MicroRNAs, Mice, HEK293 Cells, Argonaute Proteins
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