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Non-Coding RNA, Volume 10, Issue 6 (December 2024) – 5 articles

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10 pages, 591 KiB  
Commentary
LNC-ing Genetics in Mitochondrial Disease
by Rick Kamps and Emma Louise Robinson
Non-Coding RNA 2024, 10(6), 57; https://doi.org/10.3390/ncrna10060057 - 15 Nov 2024
Viewed by 295
Abstract
Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), [...] Read more.
Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber’s hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns–Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial dysfunction has been implicated in the most common current causes of mortality and morbidity, including cardiovascular disease (CVD) and cancer. Identifying key genetic contributors to both MD and secondary mitochondrial dysfunction may guide clinicians to assess the most effective treatment course and prognosis, as well as informing family members of any hereditary risk of disease transmission. Identifying underlying genetic causes of primary and secondary MD involves either genome sequencing (GS) or small targeted panel analysis of known disease-causing nuclear- or mitochondrial genes coding for mitochondria-related proteins. Due to advances in GS, the importance of long non-coding RNA (lncRNA) as functional contributors to the pathophysiology of MD is being unveiled. A limited number of studies have thus far reported the importance of lncRNAs in relation to MD causation and progression, and we are entering a new area of attention for clinical geneticists in specific rare malignancies. This commentary provides an overview of what is known about the role of lncRNAs as genetic and molecular contributors to disease pathophysiology and highlights an unmet need for a deeper understanding of mitochondrial dysfunction in serious human disease burdens. Full article
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15 pages, 547 KiB  
Review
Androgen Receptor and Non-Coding RNAs’ Interaction in Renal Cell Carcinoma
by Manal A. Hussain, Noha M. Elemam and Iman M. Talaat
Non-Coding RNA 2024, 10(6), 56; https://doi.org/10.3390/ncrna10060056 - 12 Nov 2024
Viewed by 601
Abstract
Renal cell carcinoma (RCC), the most prevalent among the urogenital cancers, accounts for around 3% of new cancer cases worldwide. Significantly, the incidence of RCC has doubled in developed world countries, ranking it as the sixth most common cancer in males, who represent [...] Read more.
Renal cell carcinoma (RCC), the most prevalent among the urogenital cancers, accounts for around 3% of new cancer cases worldwide. Significantly, the incidence of RCC has doubled in developed world countries, ranking it as the sixth most common cancer in males, who represent two-thirds of RCC cases. Males with RCC exhibit a higher mortality rate and tend to develop a more aggressive form of the disease than females. Sex-related risk factors, including lifestyle and biological variations, explain this difference. The androgen receptor (AR) oncogenic signaling pathway has been extensively studied among the biological factors that affect RCC. Recent advancements in high-throughput RNA sequencing techniques have underscored the significant roles played by noncoding-RNAs (ncRNAs), previously dismissed as “junk”. The oncogenic potential of AR is manifested through its dysregulation of the ncRNAs’ availability and function, promoting RCC tumorigenesis. This review offers a summary of the most recent findings on the role and molecular mechanisms of the AR in dysregulating the ncRNAs that play a role in the progression of RCC and the possibility of utilizing ncRNAs to target AR as a potential therapeutic strategy. Full article
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16 pages, 3683 KiB  
Article
Comparison of Three Computational Tools for the Prediction of RNA Tertiary Structures
by Frank Yiyang Mao, Mei-Juan Tu, Gavin McAllister Traber and Ai-Ming Yu
Non-Coding RNA 2024, 10(6), 55; https://doi.org/10.3390/ncrna10060055 - 8 Nov 2024
Viewed by 572
Abstract
Understanding the structures of noncoding RNAs (ncRNAs) is important for the development of RNA-based therapeutics. There are inherent challenges in employing current experimental techniques to determine the tertiary (3D) structures of RNAs with high complexity and flexibility in folding, which makes computational methods [...] Read more.
Understanding the structures of noncoding RNAs (ncRNAs) is important for the development of RNA-based therapeutics. There are inherent challenges in employing current experimental techniques to determine the tertiary (3D) structures of RNAs with high complexity and flexibility in folding, which makes computational methods indispensable. In this study, we compared the utilities of three advanced computational tools, namely RNAComposer, Rosetta FARFAR2, and the latest AlphaFold 3, to predict the 3D structures of various forms of RNAs, including the small interfering RNA drug, nedosiran, and the novel bioengineered RNA (BioRNA) molecule showing therapeutic potential. Our results showed that, while RNAComposer offered a malachite green aptamer 3D structure closer to its crystal structure, the performances of RNAComposer and Rosetta FARFAR2 largely depend upon the secondary structures inputted, and Rosetta FARFAR2 predictions might not even recapitulate the typical, inverted “L” shape tRNA 3D structure. Overall, AlphaFold 3, integrating molecular dynamics principles into its deep learning framework, directly predicted RNA 3D structures from RNA primary sequence inputs, even accepting several common post-transcriptional modifications, which closely aligned with the experimentally determined structures. However, there were significant discrepancies among three computational tools in predicting the distal loop of human pre-microRNA and larger BioRNA (tRNA fused pre-miRNA) molecules whose 3D structures have not been characterized experimentally. While computational predictions show considerable promise, their notable strengths and limitations emphasize the needs for experimental validation of predictions besides characterization of more RNA 3D structures. Full article
(This article belongs to the Section Computational Biology)
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19 pages, 1428 KiB  
Review
Extracellular Vesicle lncRNAs as Key Biomolecules for Cell-to-Cell Communication and Circulating Cancer Biomarkers
by Panagiotis Papoutsoglou and Antonin Morillon
Non-Coding RNA 2024, 10(6), 54; https://doi.org/10.3390/ncrna10060054 - 5 Nov 2024
Viewed by 528
Abstract
Extracellular vesicles (EVs) are secreted by almost every cell type and are considered carriers of active biomolecules, such as nucleic acids, proteins, and lipids. Their content can be uptaken and released into the cytoplasm of recipient cells, thereby inducing gene reprogramming and phenotypic [...] Read more.
Extracellular vesicles (EVs) are secreted by almost every cell type and are considered carriers of active biomolecules, such as nucleic acids, proteins, and lipids. Their content can be uptaken and released into the cytoplasm of recipient cells, thereby inducing gene reprogramming and phenotypic changes in the acceptor cells. Whether the effects of EVs on the physiology of recipient cells are mediated by individual biomolecules or the collective outcome of the total transferred EV content is still under debate. The EV RNA content consists of several types of RNA, such as messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA), the latter defined as transcripts longer than 200 nucleotides that do not code for proteins but have important established biological functions. This review aims to update our insights on the functional roles of EV and their cargo non-coding RNA during cancer progression, to highlight the utility of EV RNA as novel diagnostic or prognostic biomarkers in cancer, and to tackle the technological advances and limitations for EV RNA identification, integrity assessment, and preservation of its functionality. Full article
(This article belongs to the Special Issue Extracellular Vesicles and ncRNA)
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19 pages, 1045 KiB  
Review
Cardiomyopathies: The Role of Non-Coding RNAs
by Nicole Carabetta, Chiara Siracusa, Isabella Leo, Giuseppe Panuccio, Antonio Strangio, Jolanda Sabatino, Daniele Torella and Salvatore De Rosa
Non-Coding RNA 2024, 10(6), 53; https://doi.org/10.3390/ncrna10060053 - 23 Oct 2024
Viewed by 634
Abstract
Cardiomyopathies are the structural and functional disorders of the myocardium. Etiopathogenesis is complex and involves an interplay of genetic, environmental, and lifestyle factors eventually leading to myocardial abnormalities. It is known that non-coding (Nc) RNAs, including micro (mi)-RNAs and long non-coding (lnc) RNAs, [...] Read more.
Cardiomyopathies are the structural and functional disorders of the myocardium. Etiopathogenesis is complex and involves an interplay of genetic, environmental, and lifestyle factors eventually leading to myocardial abnormalities. It is known that non-coding (Nc) RNAs, including micro (mi)-RNAs and long non-coding (lnc) RNAs, play a crucial role in regulating gene expression. Several studies have explored the role of miRNAs in the development of various pathologies, including heart diseases. In this review, we analyzed various patterns of ncRNAs expressed in the most common cardiomyopathies: dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy. Understanding the role of different ncRNAs implicated in cardiomyopathic processes may contribute to the identification of potential therapeutic targets and novel risk stratification models based on gene expression. The analysis of ncRNAs may also be helpful to unveil the molecular mechanisms subtended to these diseases. Full article
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