microRNA-seq of cartilage reveals an overabundance of miR-140-3p which contains functional isomiRs.
Steven WoodsSarah CharltonKat CheungYao HaoJamie SoulLouise N ReynardNatalie CroweTracey E SwinglerAndrew J SkeltonKatarzyna A PirógColin G MilesDimitra TsompaniRobert M JacksonTamas DalmayIan M ClarkMatt J BarterDavid A YoungPublished in: RNA (New York, N.Y.) (2020)
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.
Keyphrases
- genome wide
- long non coding rna
- cell proliferation
- genome wide identification
- early onset
- poor prognosis
- transcription factor
- long noncoding rna
- single cell
- endothelial cells
- extracellular matrix
- electronic health record
- bioinformatics analysis
- dna methylation
- big data
- genome wide analysis
- rheumatoid arthritis
- induced pluripotent stem cells
- copy number
- pluripotent stem cells
- gene expression
- type diabetes
- randomized controlled trial
- high throughput
- machine learning
- binding protein
- clinical practice
- knee osteoarthritis
- artificial intelligence
- skeletal muscle