scholarly journals Multifaceted Regulation of MicroRNA Biogenesis: Essential Roles and Functional Integration in Neuronal and Glial Development

2021 ◽  
Vol 22 (13) ◽  
pp. 6765
Author(s):  
Izabela Suster ◽  
Yue Feng
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Functional Integration ◽  
Mirna Biogenesis ◽  
Circular Rnas ◽  
Mirna Processing ◽  
Endogenous Gene ◽  
Processing Enzymes ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are small, non-coding RNAs that function as endogenous gene silencers. Soon after the discovery of miRNAs, a subset of brain-enriched and brain-specific miRNAs were identified and significant advancements were made in delineating miRNA function in brain development. However, understanding the molecular mechanisms that regulate miRNA biogenesis in normal and diseased brains has become a prevailing challenge. Besides transcriptional regulation of miRNA host genes, miRNA processing intermediates are subjected to multifaceted regulation by canonical miRNA processing enzymes, RNA binding proteins (RBPs) and epitranscriptomic modifications. Further still, miRNA activity can be regulated by the sponging activity of other non-coding RNA classes, namely circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). Differential abundance of these factors in neuronal and glial lineages partly underlies the spatiotemporal expression and function of lineage-specific miRNAs. Here, we review the continuously evolving understanding of the regulation of neuronal and glial miRNA biogenesis at the transcriptional and posttranscriptional levels and the cooperativity of miRNA species in targeting key mRNAs to drive lineage-specific development. In addition, we review dysregulation of neuronal and glial miRNAs and the detrimental impacts which contribute to developmental brain disorders.

scholarly journals The effective function of circular RNA in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Ameli-Mojarad ◽  
Melika Ameli-Mojarad ◽  
Mahrooyeh Hadizadeh ◽  
Chris Young ◽  
Hosna Babini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rna ◽  
Circular Rnas ◽  
Colorectal Tumorigenesis ◽  
Non Coding Rnas ◽  
Mirna Sponges ◽  
Mechanisms Of Development

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.

scholarly journals Deciphering miRNAs’ Action through miRNA Editing

2019 ◽  
Vol 20 (24) ◽  
pp. 6249 ◽  
Author(s):  
Marta Correia de Sousa ◽  
Monika Gjorgjieva ◽  
Dobrochna Dolicka ◽  
Cyril Sobolewski ◽  
Michelangelo Foti
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Metabolic Diseases ◽  
Rna Binding Proteins ◽  
Mrna Translation ◽  
Mirna Biogenesis ◽  
Transcriptional Level ◽  
Non Coding Rnas ◽  
Mirna Editing

MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.

scholarly journals Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fei Long ◽  
Zhi Lin ◽  
Liang Li ◽  
Min Ma ◽  
Zhixing Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Future Perspectives ◽  
Cis Acting ◽  
New Class ◽  
Functional Peptides ◽  
Mirna Sponges

AbstractColorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

P5398CircRNAs deregulation in heart failure patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Greco ◽  
A Made' ◽  
M Longo ◽  
R Tikhomirov ◽  
S Castelvecchio ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Functional Characterization ◽  
Enrichment Analysis ◽  
Host Gene ◽  
Circular Rnas ◽  
Amplification Efficiency ◽  
Rna Seq ◽  
Bioinformatics Pipeline

Abstract Background Circular RNAs (circRNAs) are an emerging class of noncoding RNAs stemming from the splicing and circularization of pre-mRNAs exons. CircRNAs can regulate transcription and splicing, sequester microRNAs acting as “sponge” and inducing the respective targets, and bind to RNA binding proteins. Recently, they have been found deregulated in dilated cardiomyopathies (DCM), one of the cardiovascular diseases with the worst rate of morbidity and mortality, and whose molecular mechanisms are only partially known. Purpose Therein, we will evaluate in ischemic DCM patients the modulation of 17 circRNAs, 14 out of them obtained from literature data on DCM ischemic or not, while the other 3 were circRNAs not characterized in the heart previously. The study aims to identify circRNAs candidates for further functional characterization in DCM. In addition, as differential expression (DE) analysis is not easily performed for circRNAs in RNA-seq datasets, the validated circRNAs will be used to set up the most specific and sensitive bioinformatics pipeline for circRNA-DE analysis. Methods We designed divergent and convergent specific primers for 17 circRNAs and their host gene, respectively, and their amplification efficiency was measured by RT-qPCR. Transcripts expression was measured in left ventricle biopsies of 12 patients affected by non end-stage ischemic HF and of 12 matched controls. Results We identified cPVT1, cANKRD17, cBPTF as DE, and validated the modulation of 5 out of the 14 DCM-related circRNAs (cHIPK3, cALPK2, cPCMTD1, cNEBL, cSLC8A1), while cPDRM5, cTTN1 showed opposite modulation, which may be due to the specific disease condition. All of them were modulated differently from the respective host gene. CircRNA/miRNA interactions were predicted using Starbase 3.0. Next, mRNAs-targets of the identified miRNAs were predicted by mirDIP 4.1 and intersected with gene expression datasets of the same patients, previously obtained by microarray analysis. We found that cBPTF and cANKRD17 might sponge 12 and 2 miRNAs, respectively. Enrichment analysis of the relevant targets identified several important pathways implicated in DCM, such as MAPK, FoxO, EGFR, VEGF and Insulin/IGF pathways. In addition, deep RNA-Seq analysis that is currently ongoing and the validated circRNAs will be used to optimize the bioinformatics pipeline for circRNA DE analysis. Conclusions We identified a subset of circRNAs deregulated in ischemic HF potentially implicated in HF pathogenesis.

scholarly journals RNA Dynamics in Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5113
Author(s):  
Agnieszka Rybak-Wolf ◽  
Mireya Plass
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Neurodegenerative Disorder ◽  
Rna Binding Proteins ◽  
Current Evidence ◽  
Circular Rnas ◽  
Rna Dynamics ◽  
Age Related

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that heavily burdens healthcare systems worldwide. There is a significant requirement to understand the still unknown molecular mechanisms underlying AD. Current evidence shows that two of the major features of AD are transcriptome dysregulation and altered function of RNA binding proteins (RBPs), both of which lead to changes in the expression of different RNA species, including microRNAs (miRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs). In this review, we will conduct a comprehensive overview of how RNA dynamics are altered in AD and how this leads to the differential expression of both short and long RNA species. We will describe how RBP expression and function are altered in AD and how this impacts the expression of different RNA species. Furthermore, we will also show how changes in the abundance of specific RNA species are linked to the pathology of AD.

scholarly journals Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers

2019 ◽  
Vol 20 (16) ◽  
pp. 3926 ◽  
Author(s):  
Xing Zhao ◽  
Yujie Cai ◽  
Jianzhen Xu
Keyword(s):  
Noncoding Rna ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cancer Development ◽  
Circular Rnas ◽  
Open Questions ◽  
Circular Configuration ◽  
And Function

CircRNAs are a class of noncoding RNA species with a circular configuration that is formed by either typical spliceosome-mediated or lariat-type splicing. The expression of circRNAs is usually abnormal in many cancers. Several circRNAs have been demonstrated to play important roles in carcinogenesis. In this review, we will first provide an introduction of circRNAs biogenesis, especially the regulation of circRNA by RNA-binding proteins, then we will focus on the recent findings of circRNA molecular mechanisms and functions in cancer development. Finally, some open questions are also discussed.

scholarly journals Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1096
Author(s):  
Zhe Kong ◽  
Yali Lu ◽  
Xuechao Wan ◽  
Jun Luo ◽  
Dujian Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
The Novel ◽  
Cancer Tissues ◽  
Posttranscriptional Level

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers.

scholarly journals Dynamic regulation of HYL1 provides new insights into its multifaceted role in Arabidopsis

2018 ◽  
Author(s):  
Prakash Kumar Bhagat ◽  
Deepanjali Verma ◽  
Raghuram Badmi ◽  
Alok Krishna Sinha
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Phosphorylation Site ◽  
Terminal Region ◽  
Mirna Biogenesis ◽  
Dynamic Regulation ◽  
Double Stranded Rna ◽  
Microprocessor Complex

SummaryMicroRNAs (miRNAs) are 21 to 24 nucleotide non-coding RNAs that regulate gene expression. Biogenesis of miRNAs is fine-tuned by specialized microprocessor complex, the regulation of which is being continuously understood. Recruitment of HYL1 to the microprocessor complex is crucial for accurate primary-miRNA (pri-miRNA) processing and accumulation of mature miRNA in Arabidopsis thaliana. HYL1 is a double-stranded RNA binding protein also termed as DRB1, has two double-stranded RNA binding domain at N-terminal and a highly disordered C-terminal region. Also, the biological activity of HYL1 is dynamically regulated through transition from hyperphosphorylation to hypophosphorylation state. HYL1 is known to be phosphorylated by a MAP kinase MPK3 and SnRK2. However, the precise role of its phosphorylation are still unknown. Recently, the stability of HYL1 protein has been shown to be regulated by an unknown protease X. However, the identity of the protease and its molecular mechanisms are poorly understood. Here, we describe, three functionally important facets of HYL1, which provide a better picture of its association with molecular processes. First, we identified a conserved MPK3 phosphorylation site on HYL1 and its possible role in the miRNA biogenesis. Secondly, the C-terminal region of HYL1 displays tendencies to bind dsDNA. Lastly, the role of C-terminal region of HYL1 in the regulation of its protein stability and the regulation of miRNA biogenesis is documented. We show the unexplored role of C-terminal and hypothesize the novel functions of HYL1 in addition to miRNA biogenesis. We anticipate that the data presented in this study, will open a new dimension of understanding the role of double stranded RNA binding proteins in diverse biological processes of plants and animal.

scholarly journals The Combined Regulation of Long Non-coding RNA and RNA-Binding Proteins in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuanyuan Ding ◽  
Ruihua Yin ◽  
Shuai Zhang ◽  
Qi Xiao ◽  
Hongqin Zhao ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Specific Interaction ◽  
Clinical Issue ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Atherosclerosis is a complex disease closely related to the function of endothelial cells (ECs), monocytes/macrophages, and vascular smooth muscle cells (VSMCs). Despite a good understanding of the pathogenesis of atherosclerosis, the underlying molecular mechanisms are still only poorly understood. Therefore, atherosclerosis continues to be an important clinical issue worthy of further research. Recent evidence has shown that long non-coding RNAs (lncRNAs) and RNA-binding proteins (RBPs) can serve as important regulators of cellular function in atherosclerosis. Besides, several studies have shown that lncRNAs are partly dependent on the specific interaction with RBPs to exert their function. This review summarizes the important contributions of lncRNAs and RBPs in atherosclerosis and provides novel and comprehensible interaction models of lncRNAs and RBPs.

scholarly journals Functional Roles and Biological Mechanisms of Circular RNAs and Their Encoded Peptides in Glioma: A Narrative Review

2021 ◽  
Vol 8 (4) ◽  
pp. 157-167
Author(s):  
Seyedeh Zahra Bakhti ◽  
Sana Dadashi ◽  
Anahita Dah Pahlevan ◽  
Fatemeh Kafshresan
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Circular Rnas ◽  
Specific Expression ◽  
Diagnostic Biomarkers ◽  
Functional Roles ◽  
Non Coding Rnas ◽  
Mirna Sponges

Circular RNAs (circRNAs) are a complicated class of non-coding RNAs that have a covalently closed loop structure and are very stable and cautious. Multiple biological processes of malignancy, including tumorigenesis, development, invasion, metastasis, apoptosis, and vascularization, are disrupted by an increased number of circRNAs. Recent research has showed that circRNAs, functioning as microRNA (miRNA) sponges or protein scaffolds, interacting with RNA-binding proteins (RBPs), and autophagy regulators, affect the transcription and splicing regulation. Many circRNAs have tissue-specific expression patterns and are heavily conserved. CircRNA levels in neurons are dynamically modulated. Growing evidence suggests that circRNAs are highly abundant in neural tissues, perhaps owing to the proliferation of particular genes that promote circularization, implying that circRNA dysregulation is linked to nervous system disorders including glioma. The most widespread and deadly primary malignant brain tumor is glioma. CircRNA has a close connection to glioma, according to reported research. Here, the current knowledge about the properties of circRNAs is introduced and the biological and molecular functions of circRNAs are described. Then, the clinical association of circRNAs with glioma/glioblastoma and their level of expression and their regulatory mechanisms in tumorigenesis are discussed. Moreover, the potential of circRNAs as diagnostic biomarkers and predictors of brain cancer risk and possible therapeutic targets in medicine is examined.

Sign in / Sign up

Export Citation Format

Share Document