scholarly journals Depolarization-Associated CircRNA Regulate Neural Gene Expression and in Some Cases May Function as Templates for Translation

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Ebrahim Mahmoudi ◽  
Dylan Kiltschewskij ◽  
Chantel Fitzsimmons ◽  
Murray J. Cairns

Circular RNAs (circRNAs) are a relatively new class of RNA transcript with high abundance in the mammalian brain. Here, we show that circRNAs expression in differentiated neuroblastoma cells were significantly altered after depolarization with 107 upregulated and 47 downregulated circRNAs. This coincided with a global alteration in the expression of microRNA (miRNA) (n = 269) and mRNA (n = 1511) in depolarized cells, suggesting a regulatory axis of circRNA–miRNA–mRNA is involved in the cellular response to neural activity. In support of this, our in silico analysis revealed that the circular transcripts had the capacity to influence mRNA expression through interaction with common miRNAs. Loss-of-function of a highly expressed circRNA, circ-EXOC6B, resulted in altered expression of numerous mRNAs enriched in processes related to the EXOC6B function, suggesting that circRNAs may specifically regulate the genes acting in relation to their host genes. We also found that a subset of circRNAs, particularly in depolarized cells, were associated with ribosomes, suggesting they may be translated into protein. Overall, these data support a role for circRNAs in the modification of gene regulation associated with neuronal activity.

2019 ◽  
Vol 91 (9) ◽  
pp. 1584-1594 ◽  
Author(s):  
Md. Sajedul Islam ◽  
Md. Abdullah‐Al‐Kamran Khan ◽  
Md. Wahid Murad ◽  
Marwah Karim ◽  
Abul Bashar Mir Md. Khademul Islam

2018 ◽  
Vol 175 (21) ◽  
pp. 4121-4136 ◽  
Author(s):  
Wilhelmus E A de Witte ◽  
Joost W Versfelt ◽  
Maria Kuzikov ◽  
Solene Rolland ◽  
Victoria Georgi ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-19 ◽  
Author(s):  
Caroline Perronnet ◽  
Cyrille Vaillend

Two decades of molecular, cellular, and functional studies considerably increased our understanding of dystrophins function and unveiled the complex etiology of the cognitive deficits in Duchenne muscular dystrophy (DMD), which involves altered expression of several dystrophin-gene products in brain. Dystrophins are normally part of critical cytoskeleton-associated membrane-bound molecular scaffolds involved in the clustering of receptors, ion channels, and signaling proteins that contribute to synapse physiology and blood-brain barrier function. The utrophin gene also drives brain expression of several paralogs proteins, which cellular expression and biological roles remain to be elucidated. Here we review the structural and functional properties of dystrophins and utrophins in brain, the consequences of dystrophins loss-of-function as revealed by numerous studies in mouse models of DMD, and we discuss future challenges and putative therapeutic strategies that may compensate for the cognitive impairment in DMD based on experimental manipulation of dystrophins and/or utrophins brain expression.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hepeng Zhang ◽  
Fanyu Meng ◽  
Shuaicheng Dong

Osteosarcoma (OS) is a widely common sort among bone cancer in children, and its overall survival ratio is low. The hidden mechanism of tumor genesis, progression, and metastasis regarding osteosarcoma needed to be further investigated. Emerging studies concentrated on exploring the functional roles of circular RNAs (circRNAs) in human cancers. The present study conducted a loss-of-function experiments to explore the circSMARCA5-induced influence on OS proliferation, cell cycle, and metastasis. Moreover, our manuscript unearthed the potential mechanisms of circSMARCA5 in regulating OS progression by in silico analysis. Our findings would provide new evidence to support that circSMARCA5 could be indicated as a biomarker for OS.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhilei Zhao ◽  
Seiichiro Jinde ◽  
Shinsuke Koike ◽  
Mariko Tada ◽  
Yoshihiro Satomura ◽  
...  

Abstract Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3′ untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.


PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e97690 ◽  
Author(s):  
Verónica M. Borgonio Cuadra ◽  
Norma Celia González-Huerta ◽  
Sandra Romero-Córdoba ◽  
Alfredo Hidalgo-Miranda ◽  
Antonio Miranda-Duarte

2021 ◽  
Vol 7 (4) ◽  
pp. 74
Author(s):  
Chinmay Saha ◽  
Sayantan Laha ◽  
Raghunath Chatterjee ◽  
Nitai P. Bhattacharyya

Altered expression of protein coding gene (PCG) and long non-coding RNA (lncRNA) have been identified in SARS-CoV-2 infected cells and tissues from COVID-19 patients. The functional role and mechanism (s) of transcriptional regulation of deregulated genes in COVID-19 remain largely unknown. In the present communication, reanalyzing publicly available gene expression data, we observed that 66 lncRNA and 5491 PCG were deregulated in more than one experimental condition. Combining our earlier published results and using different publicly available resources, it was observed that 72 deregulated lncRNA interacted with 3228 genes/proteins. Many targets of deregulated lncRNA could also interact with SARS-CoV-2 coded proteins, modulated by IFN treatment and identified in CRISPR screening to modulate SARS-CoV-2 infection. The majority of the deregulated lncRNA and PCG were targets of at least one of the transcription factors (TFs), interferon responsive factors (IRFs), signal transducer, and activator of transcription (STATs), NFκB, MYC, and RELA/p65. Deregulated 1069 PCG was joint targets of lncRNA and TF. These joint targets are significantly enriched with pathways relevant for SARS-CoV-2 infection indicating that joint regulation of PCG could be one of the mechanisms for deregulation. Over all this manuscript showed possible involvement of lncRNA and mechanisms of deregulation of PCG in the pathogenesis of COVID-19.


2021 ◽  
Vol 22 (24) ◽  
pp. 13192
Author(s):  
Rosalia Battaglia ◽  
Ruben Alonzo ◽  
Chiara Pennisi ◽  
Angela Caponnetto ◽  
Carmen Ferrara ◽  
...  

In the last few years, microRNA-mediated regulation has been shown to be important in viral infections. In fact, viral microRNAs can alter cell physiology and act on the immune system; moreover, cellular microRNAs can regulate the virus cycle, influencing positively or negatively viral replication. Accordingly, microRNAs can represent diagnostic and prognostic biomarkers of infectious processes and a promising approach for designing targeted therapies. In the past 18 months, the COVID-19 infection from SARS-CoV-2 has engaged many researchers in the search for diagnostic and prognostic markers and the development of therapies. Although some research suggests that the SARS-CoV-2 genome can produce microRNAs and that host microRNAs may be involved in the cellular response to the virus, to date, not enough evidence has been provided. In this paper, using a focused bioinformatic approach exploring the SARS-CoV-2 genome, we propose that SARS-CoV-2 is able to produce microRNAs sharing a strong sequence homology with the human ones and also that human microRNAs may target viral RNA regulating the virus life cycle inside human cells. Interestingly, all viral miRNA sequences and some human miRNA target sites are conserved in more recent SARS-CoV-2 variants of concern (VOCs). Even if experimental evidence will be needed, in silico analysis represents a valuable source of information useful to understand the sophisticated molecular mechanisms of disease and to sustain biomedical applications.


2021 ◽  
Vol 11 (10) ◽  
pp. 996
Author(s):  
Catarina Guimarães-Teixeira ◽  
Daniela Barros-Silva ◽  
João Lobo ◽  
Diana Soares-Fernandes ◽  
Vera Constâncio ◽  
...  

(1) Background: Methylation of N6-adenosine (m6A) is the most abundant messenger RNA (mRNA) modification in eukaryotes. We assessed the expression profiles of m6A regulatory proteins in renal cell carcinoma (RCC) and their clinical relevance, namely, as potential biomarkers. (2) Methods: In silico analysis of The Cancer Genome Atlas (TCGA) dataset was use for evaluating the expression of the m6A regulatory proteins among RCC subtypes and select the most promising candidates for further validation. ALKBH5 and FTO transcript and protein expression were evaluated in a series of primary RCC (n = 120) and 40 oncocytomas selected at IPO Porto. (3) Results: In silico analysis of TCGA dataset disclosed altered expression of the major m6A demethylases among RCC subtypes, particularly FTO and ALKBH5. Furthermore, decreased FTO mRNA levels associated with poor prognosis in ccRCC and pRCC. In IPO Porto’s cohort, FTO and ALKBH5 transcript levels discriminated ccRCC from oncocytomas. Furthermore, FTO and ALKBH5 immunoexpression differed among RCC subtypes, with higher expression levels found in ccRCC comparatively to the other RCC subtypes and oncocytomas. (4) Conclusion: We conclude that altered expression of m6A RNA demethylases is common in RCC and seems to be subtype specific. Specifically, FTO and ALKBH5 might constitute new candidate biomarkers for RCC patient management, aiding in differential diagnosis of renal masses and prognostication.


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