microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs
| Autor: | Katarzyna A. Piróg, Robert M. Jackson, Tamas Dalmay, Matt J. Barter, Dimitra Tsompani, Sarah Charlton, Andrew J. Skelton, David Young, Kathleen Cheung, Tracey E. Swingler, Jamie Soul, Ian M. Clark, Louise N. Reynard, N. Crowe, Yao Hao, Steven Woods, Colin G. Miles |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Untranslated region
Small RNA Locus (genetics) Computational biology Biology Article MiRBase Mice 03 medical and health sciences IsomiR microRNA Animals Humans Gene Regulatory Networks 3' Untranslated Regions Molecular Biology Gene 030304 developmental biology 0303 health sciences Sequence Analysis RNA Gene Expression Profiling 030302 biochemistry & molecular biology Molecular Sequence Annotation Chondrogenesis Phenotype Up-Regulation MicroRNAs Cartilage Organ Specificity 5' Untranslated Regions |
| Zdroj: | Woods, S, Charlton, S, Cheung, K, Hao, Y, Soul, J, Reynard, L N, Crowe, N, Swingler, T E, Skelton, A J, Piróg, K A, Miles, C G, Tsompani, D, Jackson, R M, Dalmay, T, Clark, I M, Barter, M J & Young, D A 2020, ' microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs ', RNA (New York, N.Y.) . https://doi.org/10.1261/rna.075176.120 RNA |
| Popis: | MiR-140 is selectively expressed in cartilage. Deletion of the entire miR-140 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 datasets, 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. |
| Databáze: | OpenAIRE |
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