Non-coding RNA
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Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers.Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.
- Klíčová slova
- gene expression regulation, miRNA lncRNA., non-coding RNA,
- MeSH
- lidé MeSH
- mikro RNA genetika fyziologie MeSH
- nekódující RNA genetika fyziologie MeSH
- regulace genové exprese genetika fyziologie MeSH
- RNA dlouhá nekódující genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nekódující RNA MeSH
- RNA dlouhá nekódující MeSH
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.
- Klíčová slova
- SR proteins, large intervening non-coding RNA, snRNP, spliceosomes, splicing,
- MeSH
- RNA dlouhá nekódující * genetika MeSH
- sestřih RNA MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.
- Klíčová slova
- biomarker, epigenetic factors, non-coding RNA, osteoarthritis, targeted treatment,
- MeSH
- kruhová RNA MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- osteoartróza * genetika MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- mikro RNA * MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * MeSH
A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1, long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2, COL1A1, NOTCH1, MIR4673, and GNAS, and gene gain containing MALAT1 and TALAM1. Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development.
- Klíčová slova
- MALAT1, adenomas, array comparative genomic hybridization, colorectal cancer, long non-coding RNA,
- MeSH
- adenom * genetika patologie MeSH
- chromozomální nestabilita MeSH
- kolorektální nádory * genetika patologie MeSH
- lidé MeSH
- prekancerózy * genetika patologie MeSH
- RNA dlouhá nekódující * genetika MeSH
- srovnávací genomová hybridizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- MALAT1 long non-coding RNA, human MeSH Prohlížeč
- RNA dlouhá nekódující * MeSH
BACKGROUND: Lung cancer is one of the most fatal human cancers both in males and females. This type of cancer is categorized to different subtypes among them is non-small cell lung cancer (NSCLC). NSCLC accounts for about 80% of all cases. Long non-coding RNAs (lncRNAs) have been shown to influence the pathogenic course of lung cancer. However, the contribution of LINC01433 lncRNA in this type of cancer in Iranian patients is not clear. PURPOSE: In the current project, we evaluated expression of LINC01433 in 42 NSCLC samples and their paired non-tumoral tissues using quantitative real time polymerase chain reaction method. Samples were collected from patients admitted to Labbafinejad Hospital during 2016-2017. RESULTS: There was no significant difference in the expression of LINC01433 between tumoral and non-tumoral tissues (expression ratio 0.67, p = 0.42). Expression of this lncRNA was not associated with any of clinical and demographic data including age, gender, smoking history, stage or cancer subtype. CONCLUSION: Based on the similar expression levels of this lncRNA between tumoral and non-tumoral tissues and lack of association between expression levels and clinical data, this lncRNA is not a possible contributor to lung cancer in Iranian patients. However, expression analysis of this lncRNA in larger sample sizes is needed to verify our results.
- Klíčová slova
- expression, long non-coding RNA, lung cancer,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic genetika patologie MeSH
- nemalobuněčný karcinom plic genetika patologie MeSH
- plíce metabolismus MeSH
- RNA dlouhá nekódující * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Írán MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.
- Klíčová slova
- cancer, delivery systems, long non-coding RNA, microRNA, non-coding RNA, therapy,
- MeSH
- cílená molekulární terapie metody trendy MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- modely genetické MeSH
- nádory farmakoterapie genetika MeSH
- nekódující RNA genetika MeSH
- protinádorové látky terapeutické užití MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- RNA dlouhá nekódující genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nekódující RNA MeSH
- protinádorové látky MeSH
- RNA dlouhá nekódující MeSH
Cytoplasmic male sterility (CMS) is a widespread phenomenon in flowering plants caused by mitochondrial (mt) genes. CMS genes typically encode novel proteins that interfere with mt functions and can be silenced by nuclear fertility-restorer genes. Although the molecular basis of CMS is well established in a number of crop systems, our understanding of it in natural populations is far more limited. To identify CMS genes in a gynodioecious plant, Silene vulgaris, we constructed mt transcriptomes and compared transcript levels and RNA editing patterns in floral bud tissue from female and hermaphrodite full siblings. The transcriptomes from female and hermaphrodite individuals were very similar overall with respect to variation in levels of transcript abundance across the genome, the extent of RNA editing, and the order in which RNA editing and intron splicing events occurred. We found only a single genomic region that was highly overexpressed and differentially edited in females relative to hermaphrodites. This region is not located near any other transcribed elements and lacks an open-reading frame (ORF) of even moderate size. To our knowledge, this transcript would represent the first non-coding mt RNA associated with CMS in plants and is, therefore, an important target for future functional validation studies.
- Klíčová slova
- Cytoplasmic male sterility, Silene vulgaris, editing, mitochondrion, non-coding RNA, splicing, transcriptome.,
- MeSH
- editace RNA MeSH
- květy genetika růst a vývoj MeSH
- mitochondriální geny * MeSH
- nekódující RNA * MeSH
- neplodnost rostlin * MeSH
- rostlinné proteiny genetika metabolismus MeSH
- Silene genetika fyziologie MeSH
- transkriptom * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- nekódující RNA * MeSH
- rostlinné proteiny MeSH
The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2-3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as "non-coding RNAs". Earlier the non-coding RNA was considered "the dark matter of genome", or "the junk", whose genes has accumulated in our DNA during the course of evolution. Today we already know that non-coding RNAs fulfil a variety of regulatory functions in our body - they intervene into epigenetic processes from chromatin remodelling to histone methylation, or into the transcription process itself, or even post-transcription processes. Long non-coding RNAs (lncRNA) are one of the classes of non-coding RNAs that have more than 200 nucleotides in length (non-coding RNAs with less than 200 nucleotides in length are called small non-coding RNAs). lncRNAs represent a widely varied and large group of molecules with diverse regulatory functions. We can identify them in all thinkable cell types or tissues, or even in an extracellular space, which includes blood, specifically plasma. Their levels change during the course of organogenesis, they are specific to different tissues and their changes also occur along with the development of different illnesses, including atherosclerosis. This review article aims to present lncRNAs problematics in general and then focuses on some of their specific representatives in relation to the process of atherosclerosis (i.e. we describe lncRNA involvement in the biology of endothelial cells, vascular smooth muscle cells or immune cells), and we further describe possible clinical potential of lncRNA, whether in diagnostics or therapy of atherosclerosis and its clinical manifestations.Key words: atherosclerosis - lincRNA - lncRNA - MALAT - MIAT.
- MeSH
- ateroskleróza * patofyziologie MeSH
- lidé MeSH
- RNA dlouhá nekódující * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
Cardiac arrhythmias represent wide and heterogenic group of disturbances in the cardiac rhythm. Pathophysiology of individual arrhythmias is highly complex and dysfunction in ion channels/currents involved in generation or spreading of action potential is usually documented. Non-coding RNAs (ncRNAs) represent highly variable group of molecules regulating the heart expression program, including regulation of the expression of individual ion channels and intercellular connection proteins, e.g. connexins.Within this chapter, we will describe basic electrophysiological properties of the myocardium. We will focus on action potential generation and spreading in pacemaker and non-pacemaker cells, including description of individual ion channels (natrium, potassium and calcium) and their ncRNA-mediated regulation. Most of the studies have so far focused on microRNAs, thus, their regulatory function will be described into greater detail. Clinical consequences of altered ncRNA regulatory function will also be described together with potential future directions of the research in the field.
- Klíčová slova
- Arrhythmia, CACNA1C, Connexin 43, Ion channels, MicroRNA, Non-coding RNA,
- MeSH
- iontové kanály MeSH
- lidé MeSH
- mikro RNA MeSH
- nekódující RNA * MeSH
- srdce MeSH
- srdeční arytmie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- iontové kanály MeSH
- mikro RNA MeSH
- nekódující RNA * MeSH
The molecular target of mycotoxins is not fully understood. Extensive data derived from cell and animal experimental studies demonstrate that long non-coding RNAs (lncRNAs) play crucial roles in mycotoxin-induced toxicities. Mycotoxins stimulate the upregulation/downregulation of lncRNA expression, which further promote apoptosis, is related to the mTOR/FoxO signaling pathway, and contributes to tumor cell growth, death, and liver and chondrocyte damage. Moreover, lncRNA can establish interactions with NF-κB and cause immune evasion. These preliminary data suggest that lncRNAs are involved in potential upstream regulatory events and further regulate downstream apoptosis, oxidative stress, and anti-apoptotic events that affect cell death and survival. Therefore, we hypothesize that lncRNAs are potential targets of mycotoxins. Investigation of the expression of the potential target lncRNAs by mycotoxin-mediated stimulation, and exploration of the upstream and downstream relationship between lncRNA and the key proteins involved in mycotoxin toxicity, should be performed. This Hypothesis provides clues for further understanding of the molecular mechanisms of mycotoxins.
- Klíčová slova
- Long non-coding RNA, Mycotoxins, Oxidative stress, Target, Toxicity mechanism,
- MeSH
- apoptóza účinky léků MeSH
- autofagie účinky léků MeSH
- lidé MeSH
- mykotoxiny farmakologie MeSH
- nádorové buněčné linie MeSH
- oxidační stres účinky léků MeSH
- RNA dlouhá nekódující metabolismus MeSH
- únik nádoru z imunitní kontroly účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mykotoxiny MeSH
- RNA dlouhá nekódující MeSH