scholarly journals Crosstalk between MicroRNA and Oxidative Stress in Physiology and Pathology

2020 ◽  
Vol 21 (4) ◽  
pp. 1270 ◽  
Author(s):  
Antonella Fioravanti ◽  
Luigi Pirtoli ◽  
Antonio Giordano ◽  
Francesco Dotta

MicroRNAs (miRNA), are short regulatory RNA molecules that regulate gene expression by binding specific sequences within target messenger RNA (mRNA) [...]

2017 ◽  
Author(s):  
Maxime Wery ◽  
Camille Gautier ◽  
Marc Descrimes ◽  
Mayuko Yoda ◽  
Valérie Migeot ◽  
...  

ABSTRACTAntisense (as)lncRNAs can regulate gene expression but the underlying mechanisms and the different cofactors involved remain unclear. Using Native Elongating Transcript sequencing, here we show that stabilization of antisense Exo2-sensitivite IncRNAs (XUTs) results in the attenuation, at the nascent transcription level, of a subset of highly expressed genes displaying prominent promoter-proximal nucleosome depletion and histone acetylation. Mechanistic investigations on the catalase genectt1revealed that its induction following oxidative stress is impaired in Exo2-deficient cells, correlating with the accumulation of an asXUT. Interestingly, expression of this asXUT was also activated in wild-type cells upon oxidative stress, concomitant toctt1induction, indicating a potential attenuation feedback. This attenuation correlates with asXUT abundance, it is transcriptional, characterized by low RNAPII-ser5 phosphorylation, and it requires an histone deacetylase activity and the conserved Set2 histone methyltransferase. Finally, we identified Dicer as another RNA processing factor acting onctt1induction, but independently of Exo2. We propose that asXUTs could modulate the expression of their paired-sense genes when it exceeds a critical threshold, using a conserved mechanism independent of RNAi.AUTHOR SUMMARYExamples of regulatory antisense (as)lncRNAs acting on gene expression have been reported in multiple model organisms. However, despite their regulatory importance, aslncRNAs have been poorly studied, and the molecular bases for aslncRNAs-mediated regulation remain incomplete. One reason for the lack of global information on aslncRNAs appears to be their low cellular abundance. Indeed, our previous studies in budding and fission yeasts revealed that aslncRNAs are actively degraded by the Xrn1/Exo2-dependent cytoplasmic 5′-3′ RNA decay pathway. Using a combination of single-gene and genome-wide analyses in fission yeast, here we report that the stabilization of a set of Exo2-sensitive aslncRNAs correlates with attenuation of paired-sense genes transcription. Our work provides fundamental insights into the mechanism by which aslncRNAs could regulate gene expression. It also highlights for the first time that the level of sense gene transcription and the presence of specific chromatin features could define the potential of aslncRNA-mediated attenuation, raising the idea that aslncRNAs only attenuate those genes with expression levels above a “regulatory threshold”. This opens novel perspectives regarding what the potential determinants of aslncRNA-dependent regulation, as previous models in budding yeast rather proposed that aslncRNA-mediated repression is restricted to lowly expressed genes.


2018 ◽  
Vol 2 (2) ◽  
pp. 499-505
Author(s):  
Ignacio Roa

MicroRNAs (miRNAs) are a class of small RNA molecules noncoding to proteins, which regulate gene expression at post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in the body development and expression of certain diseases. Some miRNAs regulate the proliferation and differentiation of cells and tissues during odontogenesis.


2016 ◽  
Author(s):  
Betty Y-W. Chung ◽  
Michael J. Deery ◽  
Arnoud J. Groen ◽  
Julie Howard ◽  
David Baulcombe

AbstractMicroRNAs regulate gene expression as part of the RNA-induced silencing complex, where the sequence identity of the miRNA provides the specificity to the target messenger RNA, and the result is target repression. The mode of repression can be through target cleavage, RNA destabilization and/or decreased translational efficiency. Here, we provide a comprehensive global analysis of the evolutionarily distant unicellular green alga Chlamydomonas reinhardtii to quantify the effects of miRNA on protein synthesis and RNA abundance. We show that, similar to metazoan systems, miRNAs in Chlamydomonas regulate gene-expression primarily by destabilizing mRNAs. However, unlike metazoan miRNA where target site utilization localizes mainly to 3’UTRs, in Chlamydomonas utilized target sites lie predominantly within coding regions. These results demonstrate that destabilization of mRNA is the main evolutionarily conserved mode of action for miRNAs, but details of the mechanism diverge between plant and metazoan kingdoms.


2011 ◽  
Vol 2 (3) ◽  
pp. 127-134
Author(s):  
Tiia Husso ◽  
Mikko P. Turunen ◽  
Nigel Parker ◽  
Seppo Ylä-Herttuala

AbstractSmall RNAs have been shown to regulate gene transcription by interacting with the promoter region and modifying the histone code. The exact mechanism of function is still unclear but the feasibility to activate or repress endogenous gene expression with small RNA molecules has already been demonstrated in vitro and in vivo. In traditional gene therapy non-mutated or otherwise useful genes are inserted into patient's cells to treat a disease. In epigenetherapy the action of small RNAs is utilized by delivering only the small RNAs to patient's cells where they then regulate gene expression by epigenetic mechanisms. This method could be widely useful not only for basic research but also for clinical applications of small RNAs.


MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Rebecca Mathew ◽  
Valentina Mattei ◽  
Muna Al Hashmi ◽  
Sara Tomei

MicroRNAs are RNA molecules of ~22 nt length that regulate gene expression posttranscriptionally. The role of miRNAs has been reported in many cellular processes including apoptosis, cell differentiation, development and proliferation. The dysregulated expression of miRNAs has been proposed as a biomarker for the diagnosis, onset and prognosis of human diseases. The utility of miRNA profiles to identify and discriminate patients from healthy individuals is highly dependent on the sensitivity and specificity of the technologies used for their detection and the quantity and quality of starting material. In this review, we present an update of the current technologies for the extraction, QC assessment and detection of miRNAs with special focus to the most recent methods, discussing their advantages as well as their shortcomings.


Author(s):  
Qiu Chen ◽  
Lei Li ◽  
Yu Tu ◽  
Lu Zheng ◽  
Wei Liu ◽  
...  

AbstractMicroRNAs (miRNAs) regulate gene expression by inhibiting translation or targeting messenger RNA (mRNA) for degradation in a posttranscriptional fashion. In this study, we show that ectopic expression of miR-34a-5p reduces the mRNA and protein levels of Krüppel-like factor 4 (KLF4). We also demonstrate that miR-34a targets the 3′-untranslated mRNA region of KLF4 and show that overexpression of miR-34a induces a significant level of apoptosis in BNL CL.2 cells exposed to doxorubicin or 10 Gy X-ray. Our data suggest that the effects of miR-34a on apoptosis occur due to the downregulation of KLF4.


2021 ◽  
Vol 12 ◽  
Author(s):  
Junjian He ◽  
Xiaoxin Ma

Long non-coding RNAs (LncRNAs) can bind to other proteins or RNAs to regulate gene expression, and its role in tumors has been extensively studied. A common RNA binding protein, UPF1, is also a key factor in a variety of RNA decay pathways. RNA decay pathways serve to control levels of particular RNA molecules. The expression of UPF1 is often dysregulated in tumors, an observation which suggests that UPF1 contributes to development of a variety of tumors. Herein, we review evidence from studies of fourteen lncRNAs interact with UPF1. The interaction between lncRNA and UPFI provide fundamental basis for cell transformation and tumorigenic growth.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2037 ◽  
Author(s):  
Megan E. Filbin ◽  
Jeffrey S. Kieft

Communication between the 5′ and 3′ ends of a eukaryotic messenger RNA (mRNA) or viral genomic RNA is a ubiquitous and important strategy used to regulate gene expression. Although the canonical interaction between initiation factor proteins at the 5′ end of an mRNA and proteins bound to the polyadenylate tail at the 3′ end is well known, in fact there are many other strategies used in diverse ways. These strategies can involve “non-canonical” proteins, RNA structures, and direct RNA-RNA base-pairing between distal elements to achieve 5′-to-3′ communication. Likewise, the communication induced by these interactions influences a variety of processes linked to the use and fate of the RNA that contains them. Recent studies are revealing how dynamic these interactions are, possibly changing in response to cellular conditions or to link various phases of the mRNA’s life, from translation to decay. Thus, 5′-to-3′ communication is about more than just making a closed circle; the RNA elements and associated proteins are key players in controlling gene expression at the post-transcriptional level.


Neurotrauma ◽  
2018 ◽  
pp. 261-268
Author(s):  
Manish Bhomia ◽  
Nagaraja S. Balakathiresan ◽  
Kevin K. W. Wang ◽  
Barbara Knollmann-Ritschel

Traumatic brain injury (TBI) is currently considered one of the major causes of disability and death worldwide. The cellular and molecular changes of TBI pathology are dynamic and complex in nature. MicroRNAs (miRNA) are small endogenous RNA molecules that regulate gene expression at the posttranscriptional level. Several studies have shown a critical role of miRNAs in the development of long- and short-term TBI pathology. Circulating miRNAs are of great interest as blood-based biomarkers in TBI diagnosis. In this chapter, the authors review recent reports that aim to understand the role of miRNAs in TBI pathophysiology and their potential use as a therapeutic target. Additionally, the authors discuss the potential use of miRNAs as blood-based diagnostic markers for TBI and their possible association with other neurodegenerative diseases.


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