scholarly journals Coilin enhances phosphorylation and stability of DGCR8 and promotes miRNA biogenesis

2021 ◽  
pp. mbc.E21-05-0225
Author(s):  
Katheryn E. Lett ◽  
Madelyn K. Logan ◽  
Douglas M. McLaurin ◽  
Michael D. Hebert
Keyword(s):  
Noncoding Rnas ◽  
Mature Mirnas ◽  
Cajal Body ◽  
Mirna Biogenesis ◽  
Regulatory Interaction ◽  
Small Noncoding Rnas ◽  
Control Gene Expression ◽  
Processing Steps ◽  
Posttranscriptional Level

MicroRNAs (miRNAs) are ∼22 nt small noncoding RNAs that control gene expression at the posttranscriptional level through translational inhibition and destabilization of their target mRNAs. The biogenesis of miRNAs involves a series of processing steps beginning with cropping of the primary miRNA transcript by the Microprocessor complex, which is comprised of Drosha and DGCR8. Here we report a novel regulatory interaction between the Microprocessor components and coilin, the Cajal Body (CB) marker protein. Coilin knockdown causes alterations in the level of primary and mature miRNAs, let-7a and miR-34a, and their miRNA targets, HMGA2 and Notch1, respectively. We also found that coilin knockdown affects the levels of DGCR8 and Drosha in cells with (HeLa) and without (WI-38) CBs. To further explore the role of coilin in miRNA biogenesis, we conducted a series of co-immunoprecipitation experiments using coilin and DGCR8 constructs, which revealed that coilin and DGCR8 can form a complex. Additionally, our results indicate that phosphorylation of DGCR8, which has been shown to increase protein stability, is impacted by coilin knockdown. Collectively, our results implicate coilin as a member of the regulatory network governing miRNA biogenesis.

scholarly journals Development of MicroRNAs as Potential Therapeutics against Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Noraini Abd-Aziz ◽  
Nur Izyani Kamaruzman ◽  
Chit Laa Poh
Keyword(s):  
Noncoding Rnas ◽  
Cancer Growth ◽  
Cellular Regulation ◽  
Small Noncoding Rnas ◽  
Synthetic Mirnas ◽  
Vital Effects ◽  
Posttranscriptional Level ◽  
Tumor Suppressor Mirnas ◽  
Potential Therapeutics

MicroRNAs (miRNAs) are small noncoding RNAs that function at the posttranscriptional level in the cellular regulation process. miRNA expression exerts vital effects on cell growth such as cell proliferation and survival. In cancers, miRNAs have been shown to initiate carcinogenesis, where overexpression of oncogenic miRNAs (oncomiRs) or reduced expression of tumor suppressor miRNAs has been reported. In this review, we discuss the involvement of miRNAs in tumorigenesis, the role of synthetic miRNAs as either mimics or antagomirs to overcome cancer growth, miRNA delivery, and approaches to enhance their therapeutic potentials.

The Prognostic and Predictive Value of microRNAs in Patients with H. pylori-positive Gastric Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4639-4645 ◽  
Author(s):  
Seyed Mostafa Parizadeh ◽  
Reza Jafarzadeh-Esfehani ◽  
Amir Avan ◽  
Maryam Ghandehari ◽  
Fatemeh Goldani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressors ◽  
Ectopic Expression ◽  
Noncoding Rnas ◽  
World Population ◽  
Normal Flora ◽  
Small Noncoding Rnas ◽  
Control Gene Expression ◽  
The World ◽  
H Pylori

Gastric cancer (GC) has a high mortality rate with a poor 5-year survival. Helicobacter pylori (H. pylori) is present as part of the normal flora of stomach. It is found in the gastric mucosa of more than half of the world population. This bacterium is involved in developing H. pylori-induced GC due to the regulation of different micro ribonucleic acid (miRNA or miR). miRNAs are small noncoding RNAs and are recognized as prognostic biomarkers for GC that may control gene expression. miRNAs may function as tumor suppressors, or oncogenes. In this review, we evaluated studies that investigated the ectopic expression of miRNAs in the prognosis of H. pylori positive and negative GC.

scholarly journals Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Knee Osteoarthritis ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Joint Disease ◽  
Limited Information ◽  
Genetic Changes ◽  
Small Noncoding Rnas ◽  
Knee Oa ◽  
Cartilage Homeostasis

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

scholarly journals Mitochondrial microRNAs: A Putative Role in Tissue Regeneration

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte
Keyword(s):  
Tissue Regeneration ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Noncoding Rnas ◽  
Atp Synthesis ◽  
Mitochondrial Proteins ◽  
Cellular Mechanisms ◽  
Small Noncoding Rnas ◽  
Mitochondrial Ribosome

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.

Competing Endogenous RNAs in Hepatocellular Carcinoma—The Pinnacle of Rivalry

2019 ◽  
Vol 39 (04) ◽  
pp. 463-475 ◽  
Author(s):  
Abdelrahman Yousry Afify ◽  
Salma Abdulmaqsoud Ibrahim ◽  
Mennah Hisham Aldamsisi ◽  
Mai Saad Zaghloul ◽  
Nada El-Ekiaby ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Solo Performance ◽  
Regulatory Pathways ◽  
Small Noncoding Rnas ◽  
Posttranscriptional Gene Regulation ◽  
Competing Endogenous Rnas ◽  
Genomic Regulation

AbstractThe role of noncoding transcripts in gene expression is nowadays acknowledged to keep various diseases at bay—despite being referred to as “junk” DNA several years ago. Believed to be at the heart of multiple regulatory pathways, microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) involved in posttranscriptional gene regulation. Recently, the discovery of ncRNAs that compete for shared miRNA pools has dimmed the light on the solo performance of miRNAs in genomic regulation. Indeed, several studies describe RNAs such as long noncoding RNAs, mRNAs, circular RNAs, pseudogenes, and viral RNAs as competing endogenous RNAs (ceRNAs) that sequester miRNAs, allowing for de-repression of downstream miRNA targets. Such integration between coding and noncoding transcripts forms complex ceRNA networks that when dysregulated lead to several diseases such as hepatocellular carcinoma. Here, the authors review perturbed ceRNA networks in hepatocellular carcinoma, describe the role of each in tumorigenesis, and discuss their various clinical implications.

scholarly journals MicroRNAs and the regulation of aldosterone signaling in the kidney

2015 ◽  
Vol 308 (7) ◽  
pp. C521-C527 ◽  
Author(s):  
Michael B. Butterworth
Keyword(s):  
Ion Transport ◽  
Hormonal Regulation ◽  
Noncoding Rnas ◽  
Short Review ◽  
Biological Molecules ◽  
Small Noncoding Rnas ◽  
Extracellular Signaling ◽  
Corticosteroid Hormones ◽  
Mineralocorticoid Hormone

The role of small noncoding RNAs, termed microRNAs (miRs), in development and disease has been recognized for many years. The number of miRs and regulated targets that reinforce a role for miRs in human disease and disease progression is ever-increasing. However, less is known about the involvement of miRs in steady-state, nondisease homeostatic pathways. In the kidney, much of the regulated ion transport is under the control of hormonal signaling. Evidence is emerging that miRs are involved in the hormonal regulation of kidney function and, particularly, in ion transport. In this short review, the production and intra- and extracellular signaling of miRs and the involvement of miRs in kidney disease are discussed. The discussion also focuses on the role of these small biological molecules in the homeostatic control of ion transport in the kidney. MiR regulation of and by corticosteroid hormones, in particular the mineralocorticoid hormone aldosterone, is considered. While information about the role of aldosterone-regulated miRs in the kidney is limited, an increase in the research in this area will undoubtedly highlight the involvement of miRs as central mediators of hormonal signaling in normal physiology.

scholarly journals Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells

2008 ◽  
Vol 181 (7) ◽  
pp. 1055-1063 ◽  
Author(s):  
Rajini Mudhasani ◽  
Zhiqing Zhu ◽  
Gyorgy Hutvagner ◽  
Christine M. Eischen ◽  
Stephen Lyle ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mature Mirnas ◽  
Mirna Biogenesis ◽  
Premature Senescence ◽  
Primary Cells ◽  
Embryonic Fibroblasts ◽  
P53 Signaling ◽  
Adult Skin

Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis in mammals. Recent evidence indicates that Dicer and miRNA may also regulate tumorigenesis. To better characterize the role of miRNA in primary cell growth, we generated Dicer-conditional mice. Ablation of Dicer and loss of mature miRNAs in embryonic fibroblasts up-regulated p19Arf and p53 levels, inhibited cell proliferation, and induced a premature senescence phenotype that was also observed in vivo after Dicer ablation in the developing limb and in adult skin. Furthermore, deletion of the Ink4a/Arf or p53 locus could rescue fibroblasts from premature senescence induced by Dicer ablation. Although levels of Ras and Myc oncoproteins appeared unaltered, loss of Dicer resulted in increased DNA damage and p53 activity in these cells. These results reveal that loss of miRNA biogenesis activates a DNA damage checkpoint, up-regulates p19Arf-p53 signaling, and induces senescence in primary cells.

scholarly journals Looking for Pyroptosis-Modulating miRNAs as a Therapeutic Target for Improving Myocardium Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Seahyoung Lee ◽  
Eunhyun Choi ◽  
Min-Ji Cha ◽  
Ki-Chul Hwang
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Inflammatory Response ◽  
Therapeutic Target ◽  
Noncoding Rnas ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Regulated Cell Death ◽  
A Current

Pyroptosis is the most recently identified type of regulated cell death with inflammatory response and has characteristics distinct from those of apoptosis or necrosis. Recently, independent studies have reported that small noncoding RNAs termed microRNAs (miRNAs) are involved in the regulation of pyroptosis. Nevertheless, only a handful of empirical data regarding miRNA-dependent regulation of pyroptosis is currently available. This review is aimed to provide a current update on the role of miRNAs in pyroptosis and to offer suggestions for future studies probing miRNAs as a linker connecting pyroptosis to various cardiovascular diseases (CVDs) and their potential as a therapeutic target for preventing excessive cell death of myocardium during CVDs.

scholarly journals MicroRNAs in Postischemic Vascular Repair

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Andrea Caporali ◽  
Costanza Emanueli
Keyword(s):  
Inflammatory Diseases ◽  
Vascular Repair ◽  
Circulating Mirnas ◽  
Growth And Remodeling ◽  
Small Noncoding Rnas ◽  
Control Gene Expression ◽  
Reparative Process ◽  
Ischemic Diseases ◽  
Tumor Growth And Metastasis

The termangiogenesisdescribes the growth of endothelial sprouts from preexisting postcapillary venules. More recently, this term has been used to generally indicate the growth and remodeling process of the primitive vascular network into a complex network during development. In adulthood, angiogenesis is activated as a reparative process during wound healing and following ischemia, and it plays a key role in tumor growth and metastasis as well as in inflammatory diseases and diabetic retinopathy. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that negatively control gene expression of target mRNAs. In this paper, we aim at describing the role of miRNAs in postischemic angiogenesis. First, we will describe the regulation and the expression of miRNAs in endothelial cells. Then, we will analyze the role of miRNAs in postischemic vascular repair. Finally, we will discuss the role of circulating miRNAs as potential biomarkers in ischemic diseases.

scholarly journals MicroRNAs’ Involvement in Osteoarthritis and the Prospects for Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Xiao-Ming Yu ◽  
Hao-Ye Meng ◽  
Xue-Ling Yuan ◽  
Yu Wang ◽  
Quan-Yi Guo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Genetic Changes ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Cartilage Homeostasis ◽  
Target Binding ◽  
And Cartilage

Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA’s development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.

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