Projects per year
Abstract
MicroRNAs (miRs) play a vital role in governing cell function, with their levels tightly controlled at transcriptional and post-transcriptional levels. Different sets of RNA-binding proteins interact with primary miRs (pri-miRs) and precursor-miR transcripts (pre-miRs), controlling their biogenesis post-transcriptionally. The Hu antigen R (HuR)-mediated binding of Musashi homolog2 (MSI2) to the conserved terminal loop of pri-miR-7 regulates the levels of brain-enriched miR-7 formation in a tissue-specific manner. Here, we show that oleic acid (OA) inhibits the binding of proteins containing RNA recognition motifs (RRM) to the conserved terminal loop of pri-miR-7. Using electrophoretic mobility shift assays in HeLa cell extracts, we show that OA treatment disrupts pre-miR/protein complexes. Furthermore, OA rescues in vitro processing of pri-miR-7, which is otherwise blocked by HuR and MSI2 proteins. On the contrary, pri-miR-16 shows reduced processing in the presence of OA. This indicates that OA may inhibit the binding of other RRM-containing protein/s necessary for miR-16 processing. Finally, we demonstrate that OA induces mature miR-7 production in HeLa cells. Together, our results demonstrate that OA can regulate the processing of pri-miRs by remodeling their protein complexes. This provides a new tool to study RNA processing and a potential lead for small molecules that target the miR-7 biogenesis pathway.
Original language | English |
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Pages (from-to) | 1638-1649 |
Journal | Journal of Molecular Biology |
Volume | 429 |
Issue number | 11 |
Early online date | 5 May 2017 |
DOIs | |
Publication status | Published - 2 Jun 2017 |
Keywords / Materials (for Non-textual outputs)
- miR biogenesis
- miR-7
- MSI2
- HuR
- Oleic Acid (OA)
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- 5 Finished
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Core funding renewal for the Wellcome Trust Centre for Cell Biology
1/10/11 → 30/04/17
Project: Research
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Regulation of miRNA Biogenesis and function in humans
Michlewski, G.
1/01/11 → 31/12/15
Project: Research