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RNA Methylation in ncRNA: Classes, Detection, and Molecular Associations

Giulia Romano, Dario Veneziano, Giovanni Nigita, Serge P. Nana-Sinkam
2018 Frontiers in Genetics  
some cases, their function (Kawahara et al., 2007; Nigita et al., 2016) .  ...  Established RNA modifications, such as RNA editing events, have been shown to dynamically alter the sequence and/or the structure of miRNAs (Nigita et al., 2015; Nishikura, 2016) and consequently, in  ... 
doi:10.3389/fgene.2018.00243 pmid:30050561 pmcid:PMC6052889 fatcat:xkm2rcnsrjg7daowy6edino5w4

miRandola: Extracellular Circulating MicroRNAs Database

Francesco Russo, Sebastiano Di Bella, Giovanni Nigita, Valentina Macca, Alessandro Laganà, Rosalba Giugno, Alfredo Pulvirenti, Alfredo Ferro, KT. Jeang
2012 PLoS ONE  
MicroRNAs are small noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular messenger RNAs. They are frequently dysregulated in cancer and have shown great potential as tissue-based markers for cancer classification and prognostication. microRNAs are also present in extracellular human body fluids such as serum, plasma, saliva, and urine. Most of circulating microRNAs are present in human plasma and serum cofractionate
more » ... with the Argonaute2 (Ago2) protein. However, circulating microRNAs have been also found in membranebound vesicles such as exosomes. Since microRNAs circulate in the bloodstream in a highly stable, extracellular form, they may be used as blood-based biomarkers for cancer and other diseases. A knowledge base of extracellular circulating miRNAs is a fundamental tool for biomedical research. In this work, we present miRandola, a comprehensive manually curated classification of extracellular circulating miRNAs. miRandola is connected to miRò , the miRNA knowledge base, allowing users to infer the potential biological functions of circulating miRNAs and their connections with phenotypes. The miRandola database contains 2132 entries, with 581 unique mature miRNAs and 21 types of samples. miRNAs are classified into four categories, based on their extracellular form: miRNA-Ago2 (173 entries), miRNA-exosome (856 entries), miRNA-HDL (20 entries) and miRNA-circulating (1083 entries). miRandola is available online at: http://atlas.dmi.unict.it/mirandola/index. html.
doi:10.1371/journal.pone.0047786 pmid:23094086 pmcid:PMC3477145 fatcat:n7p5crxa75a7hbom5n2aubjrzi

Editorial: Epitranscriptomics: The Novel RNA Frontier

Giovanni Nigita, Mario Acunzo, William Chi Shing Cho, Carlo M. Croce
2018 Frontiers in Bioengineering and Biotechnology  
Editorial on the Research Topic Epitranscriptomics: The Novel RNA Frontier From the formulation of the Central Dogma of molecular biology to the discovery of novel noncoding RNA (ncRNAs) classes, the focus of Genetics involved DNA variants with the scope of elucidating biological pathways perturbed in disease. Recently, considerable attention has shifted toward the study of RNA modifications dynamically occurring in both protein-coding as well as non-coding RNAs, in both animal and plant
more » ... s. This, in turn, has gradually led to the exciting exploration of the novel frontier of "Epitranscriptomics, " revealing an additional, finer layer of complexity in gene regulation. The application of the fast-growing high-throughput sequencing technology (HTS) has allowed the unprecedented opportunity to unveil millions of RNA modifications in human genes, such as resulting from methylation (e.g., m6A, m1A, m5C, hm5C, 2'OMe), pseudourylation (Ψ ) and deamination (e.g., A-to-I RNA editing), counting to date more than 140 different forms of RNA modifications. The aim of this Research Topic was to collect both original research articles and reviews in addressing the bioinformatics approaches and wet lab methodologies necessary to aid in the detection of novel RNA modifications and characterization of their biological functions, as well as contribute to the identification of the molecular protagonists involved in the regulation of such phenomena. Among the articles embracing the scope of the Research Topic, we have collected five reviews, four original research and methods articles, and a technology article. Two reviews focused on RNA modifications in ncRNAs. Romano et al. surveyed the main types of RNA methylation in the context of ncRNAs with their associated functions. They also described the methodologies to identify and profile such RNA modifications. On the other hand, Zhao et al. instead, focused on the role of the pseudouridylation of ncRNAs in nuclear gene expression events. In particular, they reviewed how, in the nuclear context, ncRNA pseudouridylation contributes to transcription and pre-miRNA splicing. Another important RNA modification is the non-templated addition of uridine(s) to the terminal end of RNA, termed 3 ′ RNA uridylation, which has been described having a role in the regulation of both mRNAs and ncRNAs. In this collection, Menezes et al. reviewed current discoveries of the functional roles for 3 ′ RNA uridylation, particularly focusing on mammalian biology. RNA modifications add a novel and fine-tuning layer to gene expression regulation, having recently shown how the dysregulation of these phenomena can lead to the onset of disease, such as neurological diseases and cancer. In this collection, Angelova et al. discussed the emerging findings that show indicate the modifications of RNA impact the development of the brain and their involvement in neurological disorders. One of the most abundant internal modifications
doi:10.3389/fbioe.2018.00191 pmid:30564574 pmcid:PMC6288354 fatcat:tchzpmzwxva2tkcciwfpgjsinq

Non-Coding RNA Editing in Cancer Pathogenesis

Giulia Romano, Michela Saviana, Patricia Le, Howard Li, Lavender Micalo, Giovanni Nigita, Mario Acunzo, Patrick Nana-Sinkam
2020 Cancers  
In a recent paper by Nigita and colleagues, the investigators identified the deregulation of miRNA editing events between lung tumor and normal tissues [108] .  ... 
doi:10.3390/cancers12071845 pmid:32650588 pmcid:PMC7408896 fatcat:o5lbiqgai5buxibkgxy2wg2lva

Computational Approaches for the Analysis of ncRNA through Deep Sequencing Techniques

Dario Veneziano, Giovanni Nigita, Alfredo Ferro
2015 Frontiers in Bioengineering and Biotechnology  
The majority of the human transcriptome is defined as non-coding RNA (ncRNA), since only a small fraction of human DNA encodes for proteins, as reported by the ENCODE project. Several distinct classes of ncRNAs, such as transfer RNA, microRNA, and long non-coding RNA, have been classified, each with its own three-dimensional folding and specific function. As ncRNAs are highly abundant in living organisms and have been discovered to play important roles in many biological processes, there has
more » ... n an ever increasing need to investigate the entire ncRNAome in further unbiased detail. Recently, the advent of next-generation sequencing (NGS) technologies has substantially increased the throughput of transcriptome studies, allowing an unprecedented investigation of ncRNAs, as regulatory pathways and novel functions involving ncRNAs are now also emerging. The huge amount of transcript data produced by NGS has progressively required the development and implementation of suitable bioinformatics workflows, complemented by knowledge-based approaches, to identify, classify, and evaluate the expression of hundreds of ncRNAs in normal and pathological conditions, such as cancer. In this mini-review, we present and discuss current bioinformatics advances in the development of such computational approaches to analyze and classify the ncRNA component of human transcriptome sequence data obtained from NGS technologies.
doi:10.3389/fbioe.2015.00077 pmid:26090362 pmcid:PMC4453482 fatcat:aqkuaqsshnaubfiumoo3qzm6nm

Detecting and Characterizing A-To-I microRNA Editing in Cancer

Gioacchino P. Marceca, Luisa Tomasello, Rosario Distefano, Mario Acunzo, Carlo M. Croce, Giovanni Nigita
2021 Cancers  
To overcome this limitation, Nigita et al.  ... 
doi:10.3390/cancers13071699 pmid:33916692 fatcat:7y3kwq4x3zas5alq77bljrjhsu

Disparities in Lung Cancer: miRNA Isoform Characterization in Lung Adenocarcinoma

Rosario Distefano, Giovanni Nigita, Patricia Le, Giulia Romano, Mario Acunzo, Patrick Nana-Sinkam
2022 Cancers  
Despite the development of targeted therapeutics, immunotherapy, and strategies for early detection, lung cancer carries a high mortality. Further, significant racial disparities in outcomes exist for which the molecular drivers have yet to be fully elucidated. The growing field of Epitranscriptomics has introduced a new layer of complexity to the molecular pathogenesis of cancer. RNA modifications can occur in coding and non-coding RNAs, such as miRNAs, possibly altering their gene regulatory
more » ... unction. The potential role for such modifications as clinically informative biomarkers remains largely unknown. Here, we concurrently profiled canonical miRNAs, shifted isomiRs (templated and non-templated), and miRNAs with single-point modification events (RNA and DNA) in White American (W) and Black or African American (B/AA) lung adenocarcinoma (LUAD) patients. We found that while most deregulated miRNA isoforms were similar in W and B/AA LUAD tissues compared to normal adjacent tissues, there was a subgroup of isoforms with deregulation according to race. We specifically investigated an edited miRNA, miR-151a-3p with an A-to-I editing event at position 3, to determine how its altered expression may be associated with activation of divergent biological pathways between W and B/AA LUAD patients. Finally, we identified distinct race-specific miRNA isoforms that correlated with prognosis for both Ws and B/AAs. Our results suggested that concurrently profiling canonical and non-canonical miRNAs may have potential as a strategy for identifying additional distinct biological pathways and biomarkers in lung cancer.
doi:10.3390/cancers14030773 pmid:35159038 pmcid:PMC8833952 fatcat:qn3yhan4grdwxnpyradpiljsyq

The MicroRNA Family Gets Wider: The IsomiRs Classification and Role

Luisa Tomasello, Rosario Distefano, Giovanni Nigita, Carlo M. Croce
2021 Frontiers in Cell and Developmental Biology  
MicroRNAs (miRNAs or miRs) are the most characterized class of non-coding RNAs and are engaged in many cellular processes, including cell differentiation, development, and homeostasis. MicroRNA dysregulation was observed in several diseases, cancer included. Epitranscriptomics is a branch of epigenomics that embraces all RNA modifications occurring after DNA transcription and RNA synthesis and involving coding and non-coding RNAs. The development of new high-throughput technologies, especially
more » ... eep RNA sequencing, has facilitated the discovery of miRNA isoforms (named isomiRs) resulting from RNA modifications mediated by enzymes, such as deaminases and exonucleases, and differing from the canonical ones in length, sequence, or both. In this review, we summarize the distinct classes of isomiRs, their regulation and biogenesis, and the active role of these newly discovered molecules in cancer and other diseases.
doi:10.3389/fcell.2021.668648 pmid:34178993 pmcid:PMC8220208 fatcat:mfxgs7arsfezxa7qus4ktknumq

Knowledge in the Investigation of A-to-I RNA Editing Signals

Giovanni Nigita, Salvatore Alaimo, Alfredo Ferro, Rosalba Giugno, Alfredo Pulvirenti
2015 Frontiers in Bioengineering and Biotechnology  
Giovanni Nigita and Salvatore Alaimo have contributed equally to this work. ‡ Rosalba Giugno and Alfredo Pulvirenti have contributed equally to this work.  ... 
doi:10.3389/fbioe.2015.00018 pmid:25759810 pmcid:PMC4338823 fatcat:yjjx2hxapbcp5fzuw7p2syrltq

Exosomal miRNA signatures of pancreatic lesions

Caterina Vicentini, Federica Calore, Giovanni Nigita, Paolo Fadda, Michele Simbolo, Nicola Sperandio, Claudio Luchini, Rita T. Lawlor, Carlo Maria Croce, Vincenzo Corbo, Matteo Fassan, Aldo Scarpa
2020 BMC Gastroenterology  
Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development. A series of 140 plasma samples obtained from patients affected by pancreatic ductal adenocarcinoma (PDAC, n =
more » ... ), pancreatic neuroendocrine tumors (PanNET, n = 42), intraductal papillary mucinous neoplasms (IPMN, n = 20), and ampulla of Vater carcinomas (AVC, n = 20) were analyzed. Comprehensive miRNA profiling was performed on plasma-derived exosomes. Relevant miRNAs were validated by qRT-PCR and in situ hybridization (ISH). Lesion specific miRNAs were identified through multiple disease comparisons. Selected miRNAs were validated in the plasma by qRT-PCR and at tissue level by ISH. We leveraged the presence of clinical subtypes with each disease cohort to identify miRNAs that are differentially enriched in aggressive phenotypes. This study shows that pancreatic lesions are characterized by specific exosomal-miRNA signatures. We also provide the basis for further explorations in order to better understand the relevance of these signatures in pancreatic neoplasms.
doi:10.1186/s12876-020-01287-y pmid:32375666 pmcid:PMC7204029 fatcat:rl2hs5pwjvemxi43gogrmo6kh4

VIRGO: visualization of A-to-I RNA editing sites in genomic sequences

Rosario Distefano, Giovanni Nigita, Valentina Macca, Alessandro Laganà, Rosalba Giugno, Alfredo Pulvirenti, Alfredo Ferro
2013 BMC Bioinformatics  
RNA Editing is a type of post-transcriptional modification that takes place in the eukaryotes. It alters the sequence of primary RNA transcripts by deleting, inserting or modifying residues.
doi:10.1186/1471-2105-14-s7-s5 pmid:23815474 pmcid:PMC3837470 fatcat:oozq4czeczeknkyynvgh436ty4

MiR-124a Regulates Extracellular Vesicle Release by Targeting GTPase Rabs in Lung Cancer

Giulia Romano, Giovanni Nigita, Federica Calore, Michela Saviana, Patricia Le, Carlo M. Croce, Mario Acunzo, Patrick Nana-Sinkam
2020 Frontiers in Oncology  
Copyright © 2020 Romano, Nigita, Calore, Saviana, Le, Croce, Acunzo and Nana-Sinkam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).  ... 
doi:10.3389/fonc.2020.01454 pmid:32974168 pmcid:PMC7469878 fatcat:jf5x7gvwgnb3loj5lopxall774

MiREDiBase: a manually curated database of editing events in microRNAs [article]

Gioacchino Paolo Marceca, Rosario Distefano, Luisa Tomasello, Alessandro Laganá, Francesco Russo, Federica Calore, Giulia Romano, Marina Bagnoli, Pierluigi Gasparini, Alfredo Ferro, Mario Acunzo, Qin Ma (+2 others)
2020 bioRxiv   pre-print
MicroRNAs (miRNAs) are a class of regulatory small non-coding RNAs that modulate gene expression. As such, miRNAs are indirectly involved in most cellular mechanisms, including cell differentiation, proliferation, survival, and homeostasis. Several different mechanisms finely regulate miRNA expression levels and functions. Among these, miRNA editing is a type of epitranscriptomic modification that alters the original nucleotide sequence of selected miRNAs, possibly influencing their
more » ... al state and target-binding ability. To date, adenosine-to-inosine (A-to-I) and cytosine-to-uracil (C-to-U) RNA editing are recognized as the "canonical" editing types, with the A-to-I type being the predominant one. A comprehensive resource explicitly dedicated to miRNA editing data collection is still missing. Here we present MiREDiBase, a manually curated catalog of editing events in miRNAs. Overall, the current version includes 3059 unique A-to-I and C-to-U editing sites occurring in 626 human miRNA transcripts and three different species of non-human primates. Each editing event is provided with essential information and key relevant details, including biological sample, detection method, enzyme-dependent affinity, editing level, and biological function. Editing events in human mature miRNAs were provided with miRNA-target predictions and enrichment analysis. Minimum free energy structures were inferred for editing events falling into pre-miRNA regions, aiming to help users to interpret the biological information. MiREDiBase represents a valuable tool for cell biology and biomedical research, continuously updated, improved, and expanded with new data from the literature. MiREDiBase is available at https://ncrnaome.osumc.edu/miredibase.
doi:10.1101/2020.09.04.283689 fatcat:imi6lj36vve7vjsexntjgaw2gq

Tissue and exosomal miRNA editing in Non-Small Cell Lung Cancer

Giovanni Nigita, Rosario Distefano, Dario Veneziano, Giulia Romano, Mohammad Rahman, Kai Wang, Harvey Pass, Carlo M. Croce, Mario Acunzo, Patrick Nana-Sinkam
2018 Scientific Reports  
doi:10.1038/s41598-018-28528-1 pmid:29976955 pmcid:PMC6033928 fatcat:pt4gnwi7uvbjxdq7njkhx2mm3a

microRNA editing in seed region aligns with cellular changes in hypoxic conditions

Giovanni Nigita, Mario Acunzo, Giulia Romano, Dario Veneziano, Alessandro Laganà, Marika Vitiello, Dorothee Wernicke, Alfredo Ferro, Carlo M. Croce
2016 Nucleic Acids Research  
These authors equally contributed to the work.
doi:10.1093/nar/gkw532 pmid:27298257 pmcid:PMC4994866 fatcat:rhthnhsqjjfojldfpmp263cls4
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