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Woods, Steven, Charlton, Sarah, Cheung, Kathleen, Hao, Yao, Soul, Jamie, Reynard, Louise N., Crowe, Natalie, Swingler, Tracey E., Skelton, Andrew J., Piróg, Katarzyna A., Miles, Colin G., Tsompani, Dimitra, Jackson, Robert M., Dalmay, Tamas 
ORCID: https://orcid.org/0000-0003-1492-5429, Clark, Ian M., Barter, Matt J. and Young, David A.
(2020)
microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs.
RNA, 26 (11).
pp. 1575-1588.
ISSN 1355-8382
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Abstract
miR-140 is selectively expressed in cartilage. Deletion of the entire Mir140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology; however, the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5' and 3' end, with >99% having one of two seed sequences (5' bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes, respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3'UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes of Mir140- null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published data sets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140- 3p.1 is more functional than original consensus miR-140-3p seed containing isomiR.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Plant Sciences Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 09 Jul 2020 00:08 |
| Last Modified: | 13 Nov 2024 14:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/75976 |
| DOI: | 10.1261/rna.075176.120 |
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