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MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development.

ABSTRACT: Integrating differential RNA and miRNA expression during neuronal lineage induction of human embryonic stem cells we identified miR-934, a primate-specific miRNA that displays a stage-specific expression pattern during progenitor expansion and early neuron generation. We demonstrate the biological relevance of this finding by comparison with data from early to mid-gestation human cortical tissue. Further we find that miR-934 directly controls progenitor to neuroblast transition and impacts on neurite growth of newborn neurons. In agreement, miR-934 targets are involved in progenitor proliferation and neuronal differentiation whilst miR-934 inhibition results in profound global transcriptome changes associated with neurogenesis, axonogenesis, neuronal migration and neurotransmission. Interestingly, miR-934 inhibition affects the expression of genes associated with the subplate zone, a transient compartment most prominent in primates that emerges during early corticogenesis. Our data suggest that mir-934 is a novel regulator of early human neurogenesis with potential implications for a species-specific evolutionary role in brain function.

SUBMITTER: Prodromidou K

PROVIDER: S-EPMC7295570 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development.

Prodromidou Kanella K Vlachos Ioannis S IS Gaitanou Maria M Kouroupi Georgia G Hatzigeorgiou Artemis G AG Matsas Rebecca R

eLife 20200527

Integrating differential RNA and miRNA expression during neuronal lineage induction of human embryonic stem cells we identified miR-934, a primate-specific miRNA that displays a stage-specific expression pattern during progenitor expansion and early neuron generation. We demonstrate the biological relevance of this finding by comparison with data from early to mid-gestation human cortical tissue. Further we find that miR-934 directly controls progenitor to neuroblast transition and impacts on ne ...[more]

PMID: 32459171

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Project description:BackgroundOsteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potentially provide early biomarkers.MethodsSmall RNA sequencing was performed using synovial fluid from the metacarpophalangeal joints of both control and early osteoarthritic horses. A group of differentially expressed sncRNAs was selected for further validation through qRT-PCR using an independent cohort of synovial fluid samples from control and early osteoarthritic horses. Bioinformatic analysis was performed in order to identify putative targets of the differentially expressed microRNAs and to explore potential associations with specific biological processes.ResultsResults revealed 22 differentially expressed sncRNAs including 13 microRNAs; miR-10a, miR-223, let7a, miR-99a, miR-23b, miR-378, miR-143 (and six novel microRNAs), four small nuclear RNAs; U2, U5, U11, U12, three small nucleolar RNAs; U13, snoR38, snord96, and one small cajal body-specific RNA; scarna3. Five sncRNAs were validated; miR-223 was significantly reduced in early osteoarthritis and miR-23b, let-7a-2, snord96A and snord13 were significantly upregulated. Significant cellular actions deduced by the differentially expressed microRNAs included apoptosis (P < 0.0003), necrosis (P < 0.0009), autophagy (P < 0.0007) and inflammation (P < 0.00001). A conservatively filtered list of 57 messenger RNA targets was obtained; the top biological processes associated were regulation of cell population proliferation (P < 0.000001), cellular response to chemical stimulus (P < 0.000001) and cell surface receptor signalling pathway (P < 0.000001).ConclusionsSynovial fluid sncRNAs may be used as molecular biomarkers for early disease in equine osteoarthritic joints. The biological processes they regulate may play an important role in understanding early osteoarthritis pathogenesis. Characterising these dynamic molecular changes could provide novel insights on the process and mechanism of early osteoarthritis development and is critical for the development of new therapeutic approaches.

Project description:PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162) database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERβ and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GEO; GSM957192 TAX577740T ,GSM957194 TAX577740N, GSM957195 TAX577453T, GSM957197 TAX577453N, GSM957198 TAX577745T, GSM957200 TAX577745N, GSM957201 TAX577579T, GSM957203 TAX577579N) was used.

Dataset Information

MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development.

Publications

MicroRNA-934 is a novel primate-specific small non-coding RNA with neurogenic function during early development.

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