scholarly journals Involvement of transposable elements in neurogenesis

2020 ◽  
Vol 24 (2) ◽  
pp. 209-218
Author(s):  
R. N. Mustafin ◽  
E. K. Khusnutdinova
Keyword(s):  
Stem Cells ◽  
Transposable Elements ◽  
Human Brain ◽  
Significant Activity ◽  
Protein Coding ◽  
Neuronal Stem Cells ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Long Non Coding Rna

The article is about the role of transposons in the regulation of functioning of neuronal stem cells and mature neurons of the human brain. Starting from the first division of the zygote, embryonic development is governed by regular activations of transposable elements, which are necessary for the sequential regulation of the expression of genes specific for each cell type. These processes include differentiation of neuronal stem cells, which requires the finest tuning of expression of neuron genes in various regions of the brain. Therefore, in the hippocampus, the center of human neurogenesis, the highest transposon activity has been identified, which causes somatic mosai cism of cells during the formation of specific brain structures. Similar data were obtained in studies on experimental animals. Mobile genetic elements are the most important sources of long non-coding RNAs that are coexpressed with important brain protein-coding genes. Significant activity of long non-coding RNA was detected in the hippocampus, which confirms the role of transposons in the regulation of brain function. MicroRNAs, many of which arise from transposon transcripts, also play an important role in regulating the differentiation of neuronal stem cells. Therefore, transposons, through their own processed transcripts, take an active part in the epigenetic regulation of differentiation of neurons. The global regulatory role of transposons in the human brain is due to the emergence of protein-coding genes in evolution by their exonization, duplication and domestication. These genes are involved in an epigenetic regulatory network with the participation of transposons, since they contain nucleotide sequences complementary to miRNA and long non-coding RNA formed from transposons. In the memory formation, the role of the exchange of virus-like mRNA with the help of the Arc protein of endogenous retroviruses HERV between neurons has been revealed. A possible mechanism for the implementation of this mechanism may be reverse transcription of mRNA and site-specific insertion into the genome with a regulatory effect on the genes involved in the memory.  

Long non-coding RNAs and splicing

2021 ◽  
Author(s):  
David Staněk
Keyword(s):  
Dominant Role ◽  
Splice Sites ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Splicing Efficiency ◽  
Non Coding Rnas ◽  
Intron Removal ◽  
Long Non Coding Rna

Abstract In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.

scholarly journals Long non-coding RNA LINC00665 promotes gemcitabine resistance of Cholangiocarcinoma cells via regulating EMT and stemness properties through miR-424-5p/BCL9L axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Min Lu ◽  
Xinglei Qin ◽  
Yajun Zhou ◽  
Gang Li ◽  
Zhaoyang Liu ◽  
...  
Keyword(s):  
Acquired Resistance ◽  
Transcriptional Regulators ◽  
First Line ◽  
Protein Coding ◽  
Gemcitabine Resistance ◽  
Non Coding Rna ◽  
Sphere Formation ◽  
Long Non Coding Rna ◽  
Line Chemotherapy

AbstractGemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.

Elucidating the role of the long non-coding RNA dancr in leukemic stem cells in acute myeloid leukemia (AML)

2017 ◽  
Vol 53 ◽  
pp. S124
Author(s):  
Marius Bill ◽  
Malith Karunasiri ◽  
Matthew Burke ◽  
Allison Walker ◽  
Stefano Volinia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemic Stem Cells ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Acute Myeloid

scholarly journals LncRNAs and PRC2: Coupled Partners in Embryonic Stem Cells

Epigenomes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 14 ◽  
Author(s):  
Alessandro Fiorenzano ◽  
Emilia Pascale ◽  
Eduardo Jorge Patriarca ◽  
Gabriella Minchiotti ◽  
Annalisa Fico
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Single Cell Analysis ◽  
Embryonic Stem ◽  
Epigenetic Landscape ◽  
Polycomb Repressive Complex 2 ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Rna Genes

The power of embryonic stem cells (ESCs) lies in their ability to self-renew and differentiate. Behind these two unique capabilities is a fine-tuned molecular network that shapes the genetic, epigenetic, and epitranscriptomic ESC plasticity. Although RNA has been shown to be functionally important in only a small minority of long non-coding RNA genes, a growing body of evidence has highlighted the pivotal and intricate role of lncRNAs in chromatin remodeling. Due to their multifaceted nature, lncRNAs interact with DNA, RNA, and proteins, and are emerging as new modulators of extensive gene expression programs through their participation in ESC-specific regulatory circuitries. Here, we review the tight cooperation between lncRNAs and Polycomb repressive complex 2 (PRC2), which is intimately involved in determining and maintaining the ESC epigenetic landscape. The lncRNA-PRC2 partnership is fundamental in securing the fully pluripotent state of ESCs, which must be primed to differentiate properly. We also reflect on the advantages brought to this field of research by the advent of single-cell analysis.

The indirect antiviral potential of long non-coding RNAs encoded by IFITM pseudogenes

2021 ◽  
Author(s):  
Kazi Rahman ◽  
Alex A. Compton
Keyword(s):  
Influenza A ◽  
Virus Entry ◽  
Gene Families ◽  
Mrna Levels ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Selective Forces ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

The interferon-induced transmembrane ( IFITM ) family performs multiple functions in immunity, including inhibition of virus entry into cells. The IFITM repertoire varies widely between species and consists of protein-coding genes and pseudogenes. The selective forces driving pseudogenization within gene families are rarely understood. In this issue, the human pseudogene IFITM4P is characterized as a virus-induced, long non-coding RNA that contributes to restriction of Influenza A virus by regulating mRNA levels of IFITM1 , IFITM2 , and IFITM3 .

scholarly journals Clinical significance of long non-coding RNA DUXAP8 and its protein coding genes in hepatocellular carcinoma

2020 ◽  
Vol 11 (20) ◽  
pp. 6140-6156
Author(s):  
Xiang-Kun Wang ◽  
Xi-Wen Liao ◽  
Rui Huang ◽  
Jian-Lu Huang ◽  
Zi-Jun Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Significance ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Pre-implantation factor promotes neuroprotection by modulating long non-coding RNA H19 of the neuronal stem cells

2018 ◽  
Author(s):  
M Spinelli ◽  
S Ornaghi ◽  
A Schoeberlein ◽  
A Bordey ◽  
E Barnea ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neuronal Stem Cells ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Beyond protein-coding genes

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Anna Lozano-Ureña ◽  
Sacri R Ferrón
Keyword(s):  
Intellectual Disabilities ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rna ◽  
Neuronal Genes ◽  
Long Non Coding Rna

A long non-coding RNA called lnc-NR2F1 regulates several neuronal genes, including some involved in autism and intellectual disabilities.

scholarly journals The State of Long Non-Coding RNA Biology

2018 ◽  
Vol 4 (3) ◽  
pp. 17 ◽  
Author(s):  
John S. Mattick
Keyword(s):  
Transgenerational Inheritance ◽  
Protein Coding ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Large Numbers ◽  
Rna Biology ◽  
Subcellular Domains ◽  
Multicellular Organisms ◽  
Long Non Coding Rna

Transcriptomic studies have demonstrated that the vast majority of the genomes of mammals and other complex organisms is expressed in highly dynamic and cell-specific patterns to produce large numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Despite well characterized examples, their scaling with developmental complexity, and many demonstrations of their association with cellular processes, development and diseases, lncRNAs are still to be widely accepted as major players in gene regulation. This may reflect an underappreciation of the extent and precision of the epigenetic control of differentiation and development, where lncRNAs appear to have a central role, likely as organizational and guide molecules: most lncRNAs are nuclear-localized and chromatin-associated, with some involved in the formation of specialized subcellular domains. I suggest that a reassessment of the conceptual framework of genetic information and gene expression in the 4-dimensional ontogeny of spatially organized multicellular organisms is required. Together with this and further studies on their biology, the key challenges now are to determine the structure–function relationships of lncRNAs, which may be aided by emerging evidence of their modular structure, the role of RNA editing and modification in enabling epigenetic plasticity, and the role of RNA signaling in transgenerational inheritance of experience.

Enforced Expression Of Mir-125b Promotes the in vivo expansion Of Human Linneg cord Blood Multi-Lymphoid Progenitors and Leukemia Stem Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1648-1648
Author(s):  
Karin G. Hermans ◽  
Eric R. Lechman ◽  
Stephanie M. Dobson ◽  
Mark D. Minden ◽  
John E. Dick
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Fold Increase ◽  
Control Vector ◽  
Self Renewal ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Non Coding Rnas

Abstract Acute Myeloid Leukemia (AML) is a heterogeneous disease with a relapse rate of up to 80% depending on patient age and AML subtype. AML is organized as a functional cellular hierarchy and is sustained by a rare population of leukemia stem cells (LSC). Recent work suggests that LSC properties influence therapy response, overall survival, and disease relapse. In order to develop more effective novel therapies that target this rare cell population; it is imperative that we better understand LSCs at the molecular level. Although it is generally accepted that oncogenic mutations underlie cancer initiation and progression, most studies have focused on protein coding genes. However, there is increasing recognition that non-coding RNAs can also play a role in leukemogenesis. microRNAs (miRNA) are a family of small non-coding RNAs that function as important regulators of mRNA stability and translation of protein-coding genes with significant roles in maintenance of human hematopoietic stem cells (HSC) (Lechman et. al., Cell Stem Cell, 2012). To understand the functional role of miRNA in human hematopoiesis, we generated HSC- and leukemia stem cell (LSC)-specific microRNA (miRNA) profiles by microarray analysis of sorted cell fractions from umbilical cord blood (CB) and AML patient samples that have been validated in xenograft assays. We identified ten miRNA candidates over-represented in HSC and/or LSC. To determine whether these were functional and impacted on stem cell properties we transduced lineage depleted CB cells with lentivirus expressing either a candidate miRNA or control vector followed by transplantation into immune deficient mice. Three miRNAs (miR-125b, miR-130a, miR-155) conferred a competitive growth advantage while four miRNAs (miR-99a, miR133a, miR194, miR-196b) conferred a growth disadvantage. miR-125b, a top LSC array candidate, showed the most pronounced phenotype with an overt expansion of transduced cells (19% to 96.2%) and enlarged spleens (2.4 fold increase). Detailed flow cytometric analysis of the miR-125b human grafts in recipient mice revealed a greatly expanded proportion of multi-lymphoid progenitors (MLP), in comparison to HSC and multi-potent progenitors. Furthermore, upon enforced in vivo expression of miR-125b in three AML patient samples, we observed large increases in the primitive primitive CD34+CD117+ populations (CD34+: 2.4-4.6 fold increase; CD117+: 1.3-4.1 fold increase) and a decrease in the proportion of differentiated CD14+/CD15+ cells (CD14+: 6.2-7.6 fold decrease; CD15+: 1.2-6 fold decrease) in leukemic grafts. Limiting dilution assays into secondary recipients revealed up to a 34-fold increase in LSC frequency compared to control vector transduced AML cells. Overall, these data suggest that miR-125b normally functions in the limited self-renewal of lymphoid committed early progenitors and this function may be usurped during leukemogenesis to enhance LSC self-renewal. miR-125b belongs to an evolutionarily conserved family consisting of three paralogs (miR-125a; miR-125b1; miR-125b2). Recent studies present strong evidence for a role of the miR-125 family in normal and malignant murine hematopoiesis, yet comprehensive functional inconsistencies remain in regards to the precise roles for each paralog. We are currently carrying out additional enforced expression studies directly comparing these family members in vitro and in vivo in order to clarify the functional roles of miR-125a (a top HSC array candidate) and miR-125b (a top LSC array candidate) in both normal and malignant human hematopoiesis. These studies will determine whether the miR-125 family is a suitable target for therapy of hematological malignancies. Disclosures: No relevant conflicts of interest to declare.

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