Noncoding RNAs Dotaz Zobrazit nápovědu
Systems biology approaches, especially in the big data era, have revolutionized modern parasitology. Of the many different molecules participating in parasite-host interactions, noncoding RNAs (ncRNAs) are now known to be (i) transmitted by the vector to possibly modulate vertebrate host responses and favor vector survival and (ii) regulated in the host by parasites to favor parasite survival. Here we provide an overview of the involvement of ncRNAs in the parasite-vector-host triad and their effect on host homeostasis based on recent advances and accumulating knowledge about the role of endogenous vertebrate noncoding RNAs in vertebrate host physiology.
- Klíčová slova
- arthropod vectors, epigenetics, miRNA, noncoding RNA, parasite–vertebrate–host interaction, pathogenesis,
- MeSH
- homeostáza fyziologie MeSH
- infekce přenášené vektorem * MeSH
- interakce hostitele a parazita genetika imunologie MeSH
- lidé MeSH
- nekódující RNA genetika imunologie MeSH
- obratlovci imunologie parazitologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- nekódující RNA MeSH
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
BACKGROUND/AIM: Prediction of response to azacitidine (AZA) treatment is an important challenge in hematooncology. In addition to protein coding genes (PCGs), AZA efficiency is influenced by various noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and transposable elements (TEs). MATERIALS AND METHODS: RNA sequencing was performed in patients with myelodysplastic syndromes or acute myeloid leukemia before AZA treatment to assess contribution of ncRNAs to AZA mechanisms and propose novel disease prediction biomarkers. RESULTS: Our analyses showed that lncRNAs had the strongest predictive potential. The combined set of the best predictors included 14 lncRNAs, and only four PCGs, one circRNA, and no TEs. Epigenetic regulation and recombinational repair were suggested as crucial for AZA response, and network modeling defined three deregulated lncRNAs (CTC-482H14.5, RP11-419K12.2, and RP11-736I24.4) associated with these processes. CONCLUSION: The expression of various ncRNAs can influence the effect of AZA and new ncRNA-based predictive biomarkers can be defined.
- Klíčová slova
- Noncoding RNAs, acute myeloid leukemia, azacytidine, circular RNAs, myelodysplastic syndrome, transposable elements,
- MeSH
- akutní myeloidní leukemie * farmakoterapie genetika MeSH
- azacytidin farmakologie terapeutické užití MeSH
- epigeneze genetická MeSH
- lidé MeSH
- myelodysplastické syndromy * farmakoterapie genetika MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- azacytidin MeSH
- RNA dlouhá nekódující * MeSH
We summarize current knowledge regarding regulatory functions of long noncoding RNAs (lncRNAs) in yeast, with emphasis on lncRNAs identified recently in yeast colonies and biofilms. Potential regulatory functions of these lncRNAs in differentiated cells of domesticated colonies adapted to plentiful conditions versus yeast colony biofilms are discussed. We show that specific cell types differ in their complements of lncRNA, that this complement changes over time in differentiating upper cells, and that these lncRNAs target diverse functional categories of genes in different cell subpopulations and specific colony types.
- MeSH
- biofilmy růst a vývoj MeSH
- buněčná diferenciace MeSH
- lidé MeSH
- RNA dlouhá nekódující metabolismus MeSH
- Saccharomyces cerevisiae patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující MeSH
Prevalence of inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gut, has been on the rise in recent years-not only in the adult population but also especially in pediatric patients. Despite the absence of curative treatments, current therapeutic options are able to achieve long-term remission in a significant proportion of cases. To this end, however, there is a need for biomarkers enabling accurate diagnosis, prognosis, and prediction of response to therapies to facilitate a more individualized approach to pediatric IBD patients. In recent years, evidence has continued to evolve concerning noncoding RNAs (ncRNAs) and their roles as integral factors in key immune-related cellular pathways. Specific deregulation patterns of ncRNAs have been linked to pathogenesis of various diseases, including pediatric IBD. In this article, we provide an overview of current knowledge on ncRNAs, their altered expression profiles in pediatric IBD patients, and how these are emerging as potentially valuable clinical biomarkers as we enter an era of personalized medicine.
- Klíčová slova
- Crohn’s disease, inflammatory bowel disease, microRNA, noncoding RNA, pediatrics, ulcerative colitis,
- MeSH
- biologické markery analýza MeSH
- Crohnova nemoc genetika MeSH
- dítě MeSH
- genetické markery genetika MeSH
- idiopatické střevní záněty genetika MeSH
- individualizovaná medicína trendy MeSH
- lidé MeSH
- nekódující RNA analýza MeSH
- signální transdukce genetika MeSH
- transkriptom MeSH
- ulcerózní kolitida genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- úvodní články MeSH
- Názvy látek
- biologické markery MeSH
- genetické markery MeSH
- nekódující 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
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
Transfer RNAs acquire a large plethora of chemical modifications. Among those, modifications of the anticodon loop play important roles in translational fidelity and tRNA stability. Four human wobble U-containing tRNAs obtain 5-methoxycarbonylmethyluridine (mcm5U34) or 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), which play a role in decoding. This mark involves a cascade of enzymatic activities. The last step is mediated by alkylation repair homolog 8 (ALKBH8). In this study, we performed a transcriptome-wide analysis of the repertoire of ALKBH8 RNA targets. Using a combination of HITS-CLIP and RIP-seq analyses, we uncover ALKBH8-bound RNAs. We show that ALKBH8 targets fully processed and CCA modified tRNAs. Our analyses uncovered the previously known set of wobble U-containing tRNAs. In addition, both our approaches revealed ALKBH8 binding to several other types of noncoding RNAs, in particular C/D box snoRNAs.
- Klíčová slova
- ALKBH8, HITS-CLIP, Trm9, mcm5U, mcm5s2U, wobble uridine modification,
- MeSH
- AlkB homolog 8, tRNA methyltransferasa genetika MeSH
- antikodon MeSH
- ChiP sekvenování * MeSH
- lidé MeSH
- nekódující RNA genetika MeSH
- RNA transferová * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AlkB homolog 8, tRNA methyltransferasa MeSH
- ALKBH8 protein, human MeSH Prohlížeč
- antikodon MeSH
- nekódující RNA MeSH
- RNA transferová * MeSH
Multiple myeloma is the second most common hematological malignancy characterized by focal lesions of malignant plasma cells in the bone marrow. These lesions contain subclones that directly influence survival of patients. Bone marrow biopsies are single-site biopsies and thus cannot contain all information about the tumor. In contrast, liquid biopsies analyze circulating cells and molecules that are secreted from all sites of the tumor. Long noncoding RNA molecules are one class of these molecules. We performed a two-phase biomarker study investigating lncRNA expression profiles in exosomes of peripheral blood serum of newly diagnosed multiple myeloma (MM) patients, monoclonal gammopathy of undetermined significance (MGUS) patients in comparison with healthy donors (HD). Surprisingly, this analysis revealed dysregulation of only one exosomal lncRNA PRINS in MM vs HD. Overall, MM and MGUS patients were distinguished from HD with sensitivity of 84.9% and specificity of 83.3%. Our study suggests a possible diagnostic role for exosomal lncRNA PRINS in monoclonal gammopathies patients.
- Klíčová slova
- biomarker, long noncoding RNA, monoclonal gammopathy of undetermined significance, multiple myeloma, qPCR,
- MeSH
- dospělí MeSH
- exozómy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mnohočetný myelom * krev diagnóza mortalita MeSH
- přežití bez známek nemoci MeSH
- RNA dlouhá nekódující krev MeSH
- RNA nádorová krev 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
- klinické zkoušky MeSH
- Názvy látek
- RNA dlouhá nekódující MeSH
- RNA nádorová MeSH