Small noncoding RNAs
Dotaz
Zobrazit nápovědu
Oocyte-to-embryo transition is a process during which an oocyte ovulates, is fertilized, and becomes a developing embryo. It involves the first major genome reprogramming event in life of an organism where gene expression, which gave rise to a differentiated oocyte, is remodeled in order to establish totipotency in blastomeres of an early embryo. This remodeling involves replacement of maternal RNAs with zygotic RNAs through maternal RNA degradation and zygotic genome activation. This review is focused on expression and function of long noncoding RNAs (lncRNAs) and small RNAs during oocyte-to-embryo transition in mammals. LncRNAs are an assorted rapidly evolving collection of RNAs, which have no apparent protein-coding capacity. Their biogenesis is similar to mRNAs including transcriptional control and post-transcriptional processing. Diverse molecular and biological roles were assigned to lncRNAs although most of them probably did not acquire a detectable biological role. Since some lncRNAs serve as precursors for small noncoding regulatory RNAs in RNA silencing pathways, both types of noncoding RNA are reviewed together.
- Klíčová slova
- LTR, RNAi, lncRNA, oocyte, siRNA, zygote,
- MeSH
- blastomery chemie MeSH
- gastrulace MeSH
- lidé MeSH
- malá nekódující RNA genetika MeSH
- RNA dlouhá nekódující genetika MeSH
- savci embryologie genetika MeSH
- stabilita RNA MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- malá nekódující RNA MeSH
- RNA dlouhá nekódující MeSH
Most biochemical, computational and genetic approaches to gene finding assume the Central Dogma and look for genes that make mRNA and have ORFs. These approaches essentially do not work for one class of genes--the noncoding RNA. In all living organisms RNA is involved in a number of essential cell processes. Functional analysis of genome sequences has largely ignored RNA genes and their structures. Different RNA species including rRNA, tRNA, mRNA and sRNA (small RNA) are important structural, transfer, informational, and regulatory molecules containing complex folded conformations that participate in recognition and catalytic processes. Noncoding RNAs play an number of important structural, catalytic and regulatory roles in the cell. The size of the sRNA genes ranges from 70 to 500 nucleotides. Several transcripts of these genes are processed by RNAases and their final products are smaller. The encoding genes are localized between two ORFs and do not overlap with ORFs on the complementary DNA strand. As aptamers, some sRNA bind small molecular components (metal ions, peptides and nucleotides). This review summarizes recent data on the functions of prokaryotic sRNAs and approaches to their identification.
- MeSH
- Bacteria genetika MeSH
- bakteriální RNA * chemie genetika metabolismus MeSH
- konformace nukleové kyseliny MeSH
- molekulární modely MeSH
- molekulární sekvence - údaje MeSH
- nekódující RNA * chemie genetika metabolismus MeSH
- prokaryotické buňky metabolismus MeSH
- sekvence nukleotidů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- bakteriální RNA * MeSH
- nekódující RNA * MeSH
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers. We performed small RNA-seq in paired samples of total plasma and plasma-derived extracellular vesicles (EVs) obtained from 42 patients and 17 healthy controls and analyzed the data with respect to the stage of the disease, patient survival, response to azacitidine, mutational status, and RNA editing. Significantly higher amounts of RNA material and a striking imbalance in RNA content between plasma and EVs (more than 400 significantly deregulated sncRNAs) were found in MDS patients compared to healthy controls. Moreover, the RNA content of EV cargo was more homogeneous than that of total plasma, and different RNAs were deregulated in these two types of material. Differential expression analyses identified that many hematopoiesis-related miRNAs (e.g., miR-34a, miR-125a, and miR-150) were significantly increased in MDS and that miRNAs clustered on 14q32 were specifically increased in early MDS. Only low numbers of circulating sncRNAs were significantly associated with somatic mutations in the SF3B1 or DNMT3A genes. Survival analysis defined a signature of four sncRNAs (miR-1237-3p, U33, hsa_piR_019420, and miR-548av-5p measured in EVs) as the most significantly associated with overall survival (HR = 5.866, p < 0.001). In total plasma, we identified five circulating miRNAs (miR-423-5p, miR-126-3p, miR-151a-3p, miR-125a-5p, and miR-199a-3p) whose combined expression levels could predict the response to azacitidine treatment. In conclusion, our data demonstrate that circulating sncRNAs show specific patterns in MDS and that their expression changes during disease progression, providing a rationale for the potential clinical usefulness of circulating sncRNAs in MDS prognosis. However, monitoring sncRNA levels in total plasma or in the EV fraction does not reflect one another, instead, they seem to represent distinctive snapshots of the disease and the data should be interpreted circumspectly with respect to the type of material analyzed.
- Klíčová slova
- biomarkers, circulating small noncoding RNAs, extracellular vesicles, myelodysplastic syndromes,
- MeSH
- azacytidin farmakologie MeSH
- biologické markery krev MeSH
- biologické modely MeSH
- editace RNA genetika MeSH
- extracelulární vezikuly metabolismus MeSH
- Kaplanův-Meierův odhad MeSH
- lidé MeSH
- malá nekódující RNA krev genetika MeSH
- mikro RNA genetika metabolismus MeSH
- multivariační analýza MeSH
- mutace genetika MeSH
- myelodysplastické syndromy krev genetika patologie MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- regulace genové exprese MeSH
- reprodukovatelnost výsledků MeSH
- signální transdukce genetika MeSH
- výsledek terapie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- azacytidin MeSH
- biologické markery MeSH
- malá nekódující RNA MeSH
- mikro RNA MeSH
Many viruses appear each year. Some of these viruses result in severe disease and even death. The frequency of epidemics and pandemics is growing at an alarming rate. The lack of virus-specific etiopathogenic drugs necessitates the search for new tools for the complex treatment of severe viral diseases and their late complications. Small noncoding RNAs and their antagonists may be effective therapeutic tools for preventing virus-induced damage to targeted epithelial cells and surrounding tissues in the manifestation stage. Moreover, sncRNAs could interfere with the virus-interacting host genes that trigger the malignant transformation of target cells as a late complication of severe viral diseases.
- Klíčová slova
- ARDS, COVID-19, Cancer, SARS-CoV-2, Small noncoding RNAs,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Small non-coding RNAs (sncRNAs) are part of non-coding oligonucleotide regulators with wide physiologic and morphologic functions. They control genetic programing of cells, and may modulate processes of differentiation and death. Biogenesis of sncRNAs is now known, and some sncRNAs have been proposed as markers of malignization. Epigenetic therapy is based on the use of newly discovered genetic modifiers, such as sncRNAs, micro-RNAs, and theirs mimics. However, role of sncRNAs in structural evolution and mechanisms of adaptation is not clearly understood. Certainly, non-coding RNAs participate in processes of cellular and organismal adaptation as well as cellular and tissue structural transformation as response to changing of environmental neighbouring. Investigations into these functions of sncRNAs may be the basis of future epigenetic environmental medicine.
- Klíčová slova
- Carcinogenesis, Small non-coding RNAs, Structural evolution, Transposable elements,
- Publikační typ
- časopisecké články MeSH
- přehledy 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
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10-9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
- Klíčová slova
- association study, long noncoding RNA, pancreatic cancer, single nucleotide polymorphism,
- MeSH
- celogenomová asociační studie MeSH
- duktální karcinom slinivky břišní genetika MeSH
- genetická predispozice k nemoci MeSH
- inhibitor p15 cyklin-dependentní kinasy genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádory slinivky břišní genetika MeSH
- RNA dlouhá nekódující genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CDKN2B protein, human MeSH Prohlížeč
- inhibitor p15 cyklin-dependentní kinasy MeSH
- mikro RNA MeSH
- MIRN1256 microRNA, human MeSH Prohlížeč
- RNA dlouhá nekódující MeSH
Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.
- Klíčová slova
- RNA, metastasis, resistance to therapy, small extracellular vesicles, tumour microenvironment,
- MeSH
- extracelulární vezikuly * metabolismus MeSH
- kruhová RNA genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mezibuněčná komunikace MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové mikroprostředí * MeSH
- nádory * patologie genetika metabolismus MeSH
- RNA dlouhá nekódující genetika MeSH
- RNA genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- messenger RNA MeSH
- mikro RNA MeSH
- RNA dlouhá nekódující MeSH
- RNA MeSH
BACKGROUND: The first systematic study of small non-coding RNAs (sRNA, ncRNA) in Streptomyces is presented. Except for a few exceptions, the Streptomyces sRNAs, as well as the sRNAs in other genera of the Actinomyces group, have remained unstudied. This study was based on sequence conservation in intergenic regions of Streptomyces, localization of transcription termination factors, and genomic arrangement of genes flanking the predicted sRNAs. RESULTS: Thirty-two potential sRNAs in Streptomyces were predicted. Of these, expression of 20 was detected by microarrays and RT-PCR. The prediction was validated by a structure based computational approach. Two predicted sRNAs were found to be terminated by transcription termination factors different from the Rho-independent terminators. One predicted sRNA was identified computationally with high probability as a Streptomyces 6S RNA. Out of the 32 predicted sRNAs, 24 were found to be structurally dissimilar from known sRNAs. CONCLUSION: Streptomyces is the largest genus of Actinomyces, whose sRNAs have not been studied. The Actinomyces is a group of bacterial species with unique genomes and phenotypes. Therefore, in Actinomyces, new unique bacterial sRNAs may be identified. The sequence and structural dissimilarity of the predicted Streptomyces sRNAs demonstrated by this study serve as the first evidence of the uniqueness of Actinomyces sRNAs.
- MeSH
- algoritmy MeSH
- bakteriální RNA chemie genetika MeSH
- druhová specificita MeSH
- genom bakteriální MeSH
- intergenová DNA MeSH
- konformace nukleové kyseliny MeSH
- molekulární modely MeSH
- nekódující RNA chemie genetika MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- Streptomyces coelicolor genetika MeSH
- Streptomyces genetika MeSH
- terminátorové oblasti (genetika) MeSH
- výpočetní biologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
- Názvy látek
- bakteriální RNA MeSH
- intergenová DNA MeSH
- nekódující RNA MeSH
Verticillium nonalfalfae (V. nonalfalfae) is one of the most problematic hop (Humulus lupulus L.) pathogens, as the highly virulent fungal pathotypes cause severe annual yield losses due to infections of entire hop fields. In recent years, the RNA interference (RNAi) mechanism has become one of the main areas of focus in plant-fungal pathogen interaction studies and has been implicated as one of the major contributors to fungal pathogenicity. MicroRNA-like RNAs (milRNAs) have been identified in several important plant pathogenic fungi; however, to date, no milRNA has been reported in the V. nonalfalfae species. In the present study, using a high-throughput sequencing approach and extensive bioinformatics analysis, a total of 156 milRNA precursors were identified in the annotated V. nonalfalfae genome, and 27 of these milRNA precursors were selected as true milRNA candidates, with appropriate microRNA hairpin secondary structures. The stem-loop RT-qPCR assay was used for milRNA validation; a total of nine V. nonalfalfae milRNAs were detected, and their expression was confirmed. The milRNA expression patterns, determined by the absolute quantification approach, imply that milRNAs play an important role in the pathogenicity of highly virulent V. nonalfalfae pathotypes. Computational analysis predicted milRNA targets in the V. nonalfalfae genome and in the host hop transcriptome, and the activity of milRNA-mediated RNAi target cleavage was subsequently confirmed for two selected endogenous fungal target gene models using the 5' RLM-RACE approach.
- Klíčová slova
- RNA interference, Verticillium nonalfalfae, fungal pathogen, microRNA-like RNAs, plant-pathogen interactions,
- MeSH
- Ascomycota genetika MeSH
- fungální RNA * MeSH
- fylogeneze MeSH
- genová ontologie MeSH
- interakce hostitele a patogenu MeSH
- konformace nukleové kyseliny MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- malá nekódující RNA genetika MeSH
- mikro RNA genetika MeSH
- nemoci rostlin mikrobiologie MeSH
- regulace genové exprese u hub MeSH
- reprodukovatelnost výsledků MeSH
- stanovení celkové genové exprese MeSH
- výpočetní biologie metody MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fungální RNA * MeSH
- malá nekódující RNA MeSH
- mikro RNA MeSH