Viroids, small circular non-coding RNAs, act as infectious pathogens in higher plants, demonstrating high stability despite consisting solely of naked RNA. Their dependence of replication on host machinery poses the question of whether RNA modifications play a role in viroid biology. Here, we explore RNA modifications in the avocado sunblotch viroid (ASBVd) and the citrus exocortis viroid (CEVd), representative members of viroids replicating in chloroplasts and the nucleus, respectively, using LC - MS and Oxford Nanopore Technology (ONT) direct RNA sequencing. Although no modification was detected in ASBVd, CEVd contained approximately one m6A per RNA molecule. ONT sequencing predicted three m6A positions. Employing orthogonal SELECT method, we confirmed m6A in two positions A353 and A360, which are highly conserved among CEVd variants. These positions are located in the left terminal region of the CEVd rod-like structure where likely RNA Pol II and and TFIIIA-7ZF bind, thus suggesting potential biological role of methylation in viroid replication.

• Klíčová slova
• 6-methyladenosine, LC-MS, m6A SELECT, RNA modification, Viroid, direct RNA-seq,
• MeSH
• konformace nukleové kyseliny MeSH
• kruhová RNA * genetika   metabolismus   MeSH
• nemoci rostlin virologie   MeSH
• posttranskripční úpravy RNA * MeSH
• replikace viru MeSH
• RNA virová * genetika   metabolismus   chemie   MeSH
• sekvenční analýza RNA MeSH
• viroidy * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kruhová RNA * MeSH
• RNA virová * MeSH

In this essay, we aim to draw a short comparison between 2 important research topics - circular and circulating RNAs - and show how they are connected. The findings described here in the field of circular RNAs, which are still quite obscured by the rapidly expanding body of knowledge in biology, have added another dimension to our view of the process of gene expression, which is formed by a more complex network of molecule interactions than we previously thought. The term "circulating RNAs" refers to a broad spectrum of RNA fragments originating from different sources, such as physiologically dying cells, sites of inflammation or cancer cells, and fragments floating in human liquid tissues together with other elements. Fragments of nucleic acids circulating in blood are emerging as promising biomarkers in different medical conditions. Interestingly, circular RNAs have been found to be present in human blood and form a fraction of circulating RNAs. In addition to updating readers on these fast-developing areas of biology, we also stress the need for the study of complex networks of molecule interactions as whole structures (in unison with the thoughts of systems biology), as opposed to the trend toward searching for individual key player molecules. Fundamentally, we want to add to the rationalization and synthesis of new research findings in the scientific literature, because this direction is important not only for students, teachers and researchers, but also for the general population.

• Klíčová slova
• circular RNA, circulating RNA, complex networks, synthesis, systems biology,
• MeSH
• biologické markery MeSH
• kruhová RNA MeSH
• lidé MeSH
• racionalizace MeSH
• RNA genetika   MeSH
• systémová biologie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• kruhová RNA MeSH
• RNA MeSH

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear. MATERIAL AND METHODS: OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by the next generation sequencing (NGS), and OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa-circ-0006203 - hsa-circ-0004872, the primer design and RT-PCR were performed. The expression levels were detected by RT-qPCR. RESULTS: The NGS results demonstrated that circRNAs were abundantly expressed in OSCC, and two circRNAs were significantly differentially expressed. hsa-circ-0006203 - hsa-circ-0004872 were significantly downregulated in OSCC tissue samples and was statistically correlated with pathological differentiation. CONCLUSION: In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, it was our team who firstly explore the regulatory role of the hsa-circ-0006203 - hsa-circ-0004872 network in OSCC. The results indicated that hsa-circ-0006203 - hsa-circ-0004872 may be a potential biomarker for OSCC.

• Klíčová slova
• biomarker, circular RNA, hsa-circ-0004872, hsa-circ-0006203, oral cancer, oral carcinoma,
• MeSH
• biologické markery MeSH
• dlaždicobuněčné karcinomy hlavy a krku MeSH
• kruhová RNA genetika   metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory hlavy a krku * genetika   MeSH
• nádory úst * genetika   MeSH
• RNA genetika   metabolismus   MeSH
• spinocelulární karcinom * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• kruhová RNA MeSH
• RNA MeSH

Lung cancer is one of the main causes of cancer-related death in the world, especially due to its frequency and ineffective therapeutically approaches in the late stages of the disease. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs (circRNAs), a type of RNA with covalently closed continuous loop structures that display high structural resistance and tissue specificity pointed toward a potential biomarker role. Current investigations have identified that circRNAs have a prominent function in the regulation of oncogenic pathways, by regulating gene expression both at transcriptional and post-transcriptional level. The aim of this review is to provide novel information regarding the implications of circRNAs in lung cancer, with an emphasis on the role in disease development and progression. Initially, we explored the potential utility of circRNAs as biomarkers, focusing on function, mechanisms, and correlation with disease progression in lung cancer. Further, we will describe the interaction between circRNAs and other non-coding species of RNA (particularly microRNA) and their biological significance in lung cancer. Describing the nature of these interactions and their therapeutic potential will provide additional insight regarding the altered molecular landscape of lung cancer and consolidate the potential clinical value of these circular transcripts. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

• Klíčová slova
• biomarkers, circRNAs, lung cancer, therapeutic target,
• MeSH
• cílená molekulární terapie MeSH
• kruhová RNA chemie   genetika   MeSH
• lidé MeSH
• nádorové biomarkery * MeSH
• nádory plic farmakoterapie   genetika   metabolismus   patologie   MeSH
• regulace genové exprese u nádorů * MeSH
• RNA interference MeSH
• signální transdukce MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• kruhová RNA MeSH
• nádorové biomarkery * MeSH

Mutations in the splicing factor 3b subunit 1 (SF3B1) gene are frequent in myelodysplastic neoplasms (MDS). Because the splicing process is involved in the production of circular RNAs (circRNAs), we investigated the impact of SF3B1 mutations on circRNA processing. Using RNA sequencing, we measured circRNA expression in CD34+ bone marrow MDS cells. We defined circRNAs deregulated in a heterogeneous group of MDS patients and described increased circRNA formation in higher-risk MDS. We showed that the presence of SF3B1 mutations did not affect the global production of circRNAs; however, deregulation of specific circRNAs was observed. Particularly, we demonstrated that strong upregulation of circRNAs processed from the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor; this upregulation was exclusive to SF3B1-mutated patients and was not observed in those with mutations in other splicing factors or other recurrently mutated genes, or with other clinical variables. Furthermore, we focused on the most upregulated ZEB1-circRNA, hsa_circ_0000228, and, by its knockdown, we demonstrated that its expression is related to mitochondrial activity. Using microRNA analyses, we proposed miR-1248 as a direct target of hsa_circ_0000228. To conclude, we demonstrated that mutated SF3B1 leads to deregulation of ZEB1-circRNAs, potentially contributing to the defects in mitochondrial metabolism observed in SF3B1-mutated MDS.

• Klíčová slova
• SF3B1, ZEB1, circular RNA, myelodysplastic neoplasms, splicing,
• MeSH
• akutní myeloidní leukemie * MeSH
• fosfoproteiny genetika   MeSH
• kruhová RNA genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• myelodysplastické syndromy * genetika   MeSH
• sestřihové faktory genetika   MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfoproteiny MeSH
• kruhová RNA MeSH
• sestřihové faktory MeSH
• SF3B1 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs. However, despite the growing number of circRNAs described to date, the roles of the majority of them in hematopoiesis remain unknown. Given their stability and disease-specific expression, circRNAs have been acknowledged as novel promising biomarkers and therapeutic targets. In this paper, the biogenesis, characteristics, and roles of circRNAs are reviewed with an emphasis on their currently recognized or presumed involvement in hematopoiesis, especially in acute myeloid leukemia and myelodysplastic syndrome.

• Klíčová slova
• acute myeloid leukemia, circular RNAs, hematopoiesis, myelodysplastic syndrome,
• MeSH
• akutní myeloidní leukemie krev   genetika   MeSH
• hematopoéza * MeSH
• kruhová RNA krev   genetika   MeSH
• lidé MeSH
• myelodysplastické syndromy krev   genetika   MeSH
• nádorové biomarkery krev   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kruhová RNA MeSH
• nádorové biomarkery MeSH

BACKGROUND: Current experimental data on RNA interactions remain limited, particularly for non-coding RNAs, many of which have only recently been discovered and operate within complex regulatory networks. Researchers often rely on in-silico interaction detection algorithms, such as TargetScan, which are based on biochemical sequence alignment. However, these algorithms have limited performance. RNA-seq expression data can provide valuable insights into regulatory networks, especially for understudied interactions such as circRNA-miRNA-mRNA. By integrating RNA-seq data with prior interaction networks obtained experimentally or through in-silico predictions, researchers can discover novel interactions, validate existing ones, and improve interaction prediction accuracy. RESULTS: This paper introduces Pi-GMIFS, an extension of the generalized monotone incremental forward stagewise (GMIFS) regression algorithm that incorporates prior knowledge. The algorithm first estimates prior response values through a prior-only regression, interpolates between these prior values and the original data, and then applies the GMIFS method. Our experimental results on circRNA-miRNA-mRNA regulatory interaction networks demonstrate that Pi-GMIFS consistently enhances precision and recall in RNA interaction prediction by leveraging implicit information from bulk RNA-seq expression data, outperforming the initial prior knowledge. CONCLUSION: Pi-GMIFS is a robust algorithm for inferring acyclic interaction networks when the variable ordering is known. Its effectiveness was confirmed through extensive experimental validation. We proved that RNA-seq data of a representative size help infer previously unknown interactions available in TarBase v9 and improve the quality of circRNA disease annotation.

• Klíčová slova
• Bayesian network, Circular RNA, Functional annotation, Penalized regression, Structure inference,
• MeSH
• algoritmy MeSH
• genové regulační sítě MeSH
• kruhová RNA * genetika   metabolismus   MeSH
• lidé MeSH
• lineární modely MeSH
• messenger RNA * genetika   metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• sekvenční analýza RNA metody   MeSH
• sekvenování transkriptomu * metody   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kruhová RNA * MeSH
• messenger RNA * MeSH
• mikro RNA * MeSH

Circular dichroism (CD) is remarkably sensitive to the conformational states of nucleic acids; therefore, CD spectroscopy has been used to study most features of DNA and RNA structures. Quadruplexes are among the significant noncanonical nucleic acids architectures that have received special attentions recently. This article presents examples on the contribution of CD spectroscopy to our knowledge of quadruplex structures and their polymorphism. The examples were selected to demonstrate the potential of this simple method in the quadruplex field. As CD spectroscopy detects only the global feature of a macromolecule, it should preferably be used in combination with other techniques. On the other hand, CD spectroscopy, often as a pioneering approach, can reveal the formation of particular structural arrangements, to search for the conditions stabilizing the structures, to follow the transitions between various structural states, to explore kinetics of their appearance, to determine thermodynamic parameters and also detect formation of higher order structures. This article aims to show that CD spectroscopy is an important complementary technique to NMR spectroscopy and X-ray diffraction in quadruplex studies.

• MeSH
• cirkulární dichroismus metody   MeSH
• difrakce rentgenového záření MeSH
• DNA chemie   MeSH
• G-kvadruplexy * MeSH
• guanin chemie   MeSH
• kinetika MeSH
• konformace nukleové kyseliny * MeSH
• oligonukleotidy chemie   MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• DNA MeSH
• guanin MeSH
• oligonukleotidy 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

BACKGROUND: Early detection of colorectal cancer (CRC) significantly improves its management and patients' survival. Circular RNAs (circRNAs) are peculiar covalently closed transcripts involved in gene expression modulation whose dysregulation has been extensively reported in CRC cells. However, little is known about their alterations in the early phases of colorectal carcinogenesis. METHODS: In this study, we performed an integrative analysis of circRNA profiles in RNA-sequencing (RNA-Seq) data of 96 colorectal cancers, 27 adenomas, and matched adjacent mucosa tissues. We also investigated the levels of cognate linear transcripts and those of regulating RNA-binding proteins (RBPs). Levels of circRNA-interacting microRNAs (miRNAs) were explored by integrating data of small RNA-Seq performed on the same samples. RESULTS: Our results revealed a significant dysregulation of 34 circRNAs (paired adj. p < 0.05), almost exclusively downregulated in tumor tissues and, prevalently, in early disease stages. This downregulation was associated with decreased expression of circRNA host genes and those encoding for RBPs involved in circRNA biogenesis, including NOVA1, RBMS3, and MBNL1. Guilt-by-association analysis showed that dysregulated circRNAs correlated with increased predicted activity of cell proliferation, DNA repair, and c-Myc signaling pathways. Functional analysis showed interactions among dysregulated circRNAs, RBPs, and miRNAs, which were supported by significant correlations among their expression levels. Findings were validated in independent cohorts and public datasets, and the downregulation of circLPAR1(2,3) and circLINC00632(5) was validated by ddPCR. CONCLUSIONS: These results support that multiple altered regulatory mechanisms may contribute to the reduction of circRNA levels that characterize early colorectal carcinogenesis.

• Klíčová slova
• Adenoma, Circular RNAs, Colorectal cancer, Precancerous lesions, RNA-binding proteins, RNA-sequencing,
• Publikační typ
• časopisecké články MeSH