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

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kanella Prodromidou ◽  
Ioannis S Vlachos ◽  
Maria Gaitanou ◽  
Georgia Kouroupi ◽  
Artemis G Hatzigeorgiou ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Neurite Growth ◽  
Specific Expression ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Neuronal Lineage ◽  
Newborn Neurons ◽  
Specific Expression Pattern ◽  
Species Specific ◽  
Early Human

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.

scholarly journals Long Non-Coding RNAs in Kidney Disease

2019 ◽  
Vol 20 (13) ◽  
pp. 3276 ◽  
Author(s):  
Michael Ignarski ◽  
Rashidul Islam ◽  
Roman-Ulrich Müller
Keyword(s):  
Kidney Disease ◽  
Protein Function ◽  
Current Knowledge ◽  
Specific Expression ◽  
Non Coding Rna ◽  
Health And Disease ◽  
Non Coding Rnas ◽  
Specific Expression Pattern ◽  
Coding Potential ◽  
Simple Definition

Non-coding RNA species contribute more than 90% of all transcripts and have gained increasing attention in the last decade. One of the most recent members of this group are long non-coding RNAs (lncRNAs) which are characterized by a length of more than 200 nucleotides and a lack of coding potential. However, in contrast to this simple definition, lncRNAs are heterogenous regarding their molecular function—including the modulation of small RNA and protein function, guidance of epigenetic modifications and a role as enhancer RNAs. Furthermore, they show a highly tissue-specific expression pattern. These aspects already point towards an important role in cellular biology and imply lncRNAs as players in development, health and disease. This view has been confirmed by numerous publications from different fields in the last years and has raised the question as to whether lncRNAs may be future therapeutic targets in human disease. Here, we provide a concise overview of the current knowledge on lncRNAs in both glomerular and tubulointerstitial kidney disease.

Control of the migratory pathway of facial branchiomotor neurones

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5297-5307 ◽  
Author(s):  
S. Garel ◽  
M. Garcia-Dominguez ◽  
P. Charnay
Keyword(s):  
Expression Pattern ◽  
Close Correlation ◽  
Changing Environment ◽  
Specific Expression ◽  
Expression Of Genes ◽  
Cell Membrane Proteins ◽  
Genes Encoding ◽  
Specific Expression Pattern ◽  
And Control ◽  
Migratory Pathway

Facial branchiomotor (fbm) neurones undergo a complex migration in the segmented mouse hindbrain. They are born in the basal plate of rhombomere (r) 4, migrate caudally through r5, and then dorsally and radially in r6. To study how migrating cells adapt to their changing environment and control their pathway, we have analysed this stereotyped migration in wild-type and mutant backgrounds. We show that during their migration, fbm neurones regulate the expression of genes encoding the cell membrane proteins TAG-1, Ret and cadherin 8. Specific combinations of these markers are associated with each migratory phase in r4, r5 and r6. In Krox20 and kreisler mutant mouse embryos, both of which lack r5, fbm neurones migrate dorsally into the anteriorly positioned r6 and adopt an r6-specific expression pattern. In embryos deficient for Ebf1, a gene normally expressed in fbm neurones, part of the fbm neurones migrate dorsally within r5. Accordingly, fbm neurones prematurely express a combination of markers characteristic of an r6 location. These data suggest that fbm neurones adapt to their changing environment by switching on and off specific genes, and that Ebf1 is involved in the control of these responses. In addition, they establish a close correlation between the expression pattern of fbm neurones and their migratory behaviour, suggesting that modifications in gene expression participate in the selection of the local migratory pathway.

scholarly journals Potential Biomarkers of miR-371–373 Gene Cluster in Tumorigenesis

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 984
Author(s):  
Junaid Ali Shah ◽  
Saadullah Khattak ◽  
Mohd Ahmar Rauf ◽  
Yong Cai ◽  
Jingji Jin
Keyword(s):  
Cancer Diagnosis ◽  
Embryonic Stem ◽  
Mature Mirnas ◽  
Untranslated Regions ◽  
Mirna Cluster ◽  
Rna Transcripts ◽  
Complementary Sequences ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Potential Applications

microRNAs (miRNAs) are small non-coding RNA transcripts (20–24 nucleotides) that bind to their complementary sequences in the 3′-untranslated regions (3′-UTR) of targeted genes to negatively or positively regulate their expression. miRNAs affect the expression of genes in cells, thereby contributing to several important biological processes, including tumorigenesis. Identifying the miRNA cluster as a human embryonic stem cell (hESC)-specific miRNAs initially led to the identification of miR-371, miR-372, miR-373, and miR-373*, which can ultimately be translated into mature miRNAs. Recent evidence suggests that miR-371–373 genes are abnormally expressed in various cancers and act either as oncogenes or tumor suppressors, indicating they may be suitable as molecular biomarkers for cancer diagnosis and prevention. In this article, we summarize recent studies linking miR-371–373 functions to tumorigenesis and speculate on the potential applications of miR-371–373 as biomarkers for cancer diagnosis and treatment.

scholarly journals Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

2021 ◽  
Author(s):  
Jeffrey R. Haswell ◽  
Kaia Mattioli ◽  
Chiara Gerhardinger ◽  
Philipp G. Maass ◽  
Daniel J. Foster ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Functional Screening ◽  
Specific Expression ◽  
Endoderm Differentiation ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Clustering Approach ◽  
Non Coding Rnas ◽  
Hesc Lines ◽  
Long Non Coding Rna

ABSTRACTAlthough many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage.

Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells

Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 881-894 ◽  
Author(s):  
Y.I. Yeom ◽  
G. Fuhrmann ◽  
C.E. Ovitt ◽  
A. Brehm ◽  
K. Ohbo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Germ Cells ◽  
Regulatory Element ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Preimplantation Embryos ◽  
Specific Expression ◽  
Embryonic Germ Cells ◽  
Specific Expression Pattern

The totipotent stem cells of the pregastrulation mouse embryo which give rise to all embryonic somatic tissues and germ cells express Oct-4. The expression is downregulated during gastrulation and is thereafter only maintained in the germline lineage. Oct-4/lacZ transgenes were used to determine how this pattern of expression was achieved, and resulted in the identification of two separate regulatory elements. The distal element drives Oct-4 expression in preimplantation embryos, in migratory and postmigratory primordial germ cells but is inactive in cells of the epiblast. In cell lines this element is specifically active in embryonic stem and embryonic germ cells. The proximal element directs the epiblast-specific expression pattern, including downregulation during gastrulation; in cell lines its activity is restricted to epiblast-derived cells. Thus, Oct-4 expression in the germline is regulated separately from epiblast expression. This provides the first marker for the identification of totipotent cells in the embryo, and suggests that expression of Oct-4 in the totipotent cycle is dependent on a set of factors unique to the germline.

scholarly journals A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Meng Amy Li ◽  
Paulo P Amaral ◽  
Priscilla Cheung ◽  
Jan H Bergmann ◽  
Masaki Kinoshita ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Embryonic Stem ◽  
Rapid Progression ◽  
Lineage Specification ◽  
Nanog Expression ◽  
Non Coding Rna ◽  
A Cell ◽  
Species Specific ◽  
Long Non Coding Rna

Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of Eprn, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of Eprn or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. Eprn illustrates how lncRNAs may introduce species-specific network modulations.

scholarly journals Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0252848
Author(s):  
Jeffrey R. Haswell ◽  
Kaia Mattioli ◽  
Chiara Gerhardinger ◽  
Philipp G. Maass ◽  
Daniel J. Foster ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Functional Screening ◽  
Specific Expression ◽  
Endoderm Differentiation ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Clustering Approach ◽  
Non Coding Rnas ◽  
Hesc Lines ◽  
Long Non Coding Rna

Although many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage.

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

Identification and expression analysis of Dazl homologue in Cynops cyanurus

Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Yinjiao Zhao ◽  
Ya Du ◽  
Qinglan Ge ◽  
Fang Yan ◽  
Shu Wei
Keyword(s):  
Phylogenetic Analysis ◽  
Comparative Studies ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Specific Expression ◽  
Recognition Motif ◽  
Deleted In Azoospermia ◽  
Specific Expression Pattern

Summary The Dazl (deleted in azoospermia-like) gene encodes an RNA-binding protein containing an RNA recognition motif (RRM) and a DAZ motif. Dazl is essential for gametogenesis in vertebrates. In this study, we report the cloning of Dazl cDNA from Cynops cyanurus. Ccdazl mRNA showed a germline-specific expression pattern as expected. Ccdazl expression gradually decreased during oogenesis, suggesting that it may be involved in oocyte development. Phylogenetic analysis revealed that the Ccdazl protein shares conserved motifs/domains with Dazl proteins from other species. Cloning of Ccdazl provides a new tool to carry out comparative studies of germ cell development in amphibians.

scholarly journals Identification of the conserved long non-coding RNAs in myogenesis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anupam Bhattacharya ◽  
Simang Champramary ◽  
Tanya Tripathi ◽  
Debajit Thakur ◽  
Ilya Ioshikhes ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Muscle Development ◽  
Three Dimensional ◽  
C2c12 Cells ◽  
Mouse Muscle ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Topologically Associated Domains

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

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