Article
Biochemistry & Molecular Biology
Afshin Moradi, Paul Whatmore, Samaneh Farashi, Roberto A. Barrero, Jyotsna Batra
Summary: This study presents the isomiR-eQTL database, which helps researchers identify SNPs that can impact miRNA and isomiR expression. This database provides a foundation for the development of personalized medicine models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Noora Puhakka, Shalini Das Gupta, Niina Vuokila, Asla Pitkanen
Summary: Neuroinflammation is a secondary injury mechanism that evolves in the brain for months after traumatic brain injury (TBI). This study found that altered small non-coding RNA (sncRNA) signature, especially dysregulation of miRNAs, plays a key role in modulating post-TBI secondary injury and neuroinflammation. These findings contribute to the development of better strategies for treating TBI and neuroinflammation.
Article
Multidisciplinary Sciences
Stepan Nersisyan, Aleksandra Gorbonos, Alexey Makhonin, Anton Zhiyanov, Maxim Shkurnikov, Alexander Tonevitsky
Summary: Inaccurate cleavage of pri and pre-miRNA hairpins by Drosha and Dicer leads to the generation of miRNA isoforms known as isomiRs. 5'-isomiRs, which have variations at the 5' end, have different seed regions and distinct targetomes, adding a new dimension to miRNA research. The isomiRTar portal was developed to analyze expression profiles and targeting activity of 5'-isomiRs in cancer. Using sequencing data from the Cancer Genome Atlas, a list of 1022 5'-isomiRs expressed in 9282 tumor samples across 31 cancer types was compiled. Co-expression analysis and target prediction were performed to identify isomiR-target pairs with significant negative correlations. The analysis revealed both cancer-specific and cancer-conserved 5'-isomiR expression landscapes, and potential tumor suppressor isomiRs were identified in colorectal cancer.
Article
Biochemical Research Methods
Jose Francisco Sanchez Herrero, Raquel Pluvinet, Antonio Luna de Haro, Lauro Sumoy
Summary: The study revealed the presence of true isomiRs and artificial differences caused by sequencing errors in small RNA sequencing data, highlighting the importance of accurately identifying true isomiRs.
BMC BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Stepan Nersisyan, Anton Zhiyanov, Narek Engibaryan, Diana Maltseva, Alexander Tonevitsky
Summary: This study aims to assess the validity of a widely used procedure for selecting significant miRNA-mRNA or isomiR-mRNA pairs by comparing the correlation between their expression levels. The results show that there is a significant negative correlation between isomiR-mRNA expression levels more often in predicted targets compared to non-targets. Additionally, there are strong cancer subtype-specific patterns of isomiR activity.
FRONTIERS IN GENETICS
(2022)
Article
Plant Sciences
Pedro Perdiguero, Andreia Santos Rodrigues, Ines Chaves, Bruno Costa, Ana Alves, Nuria de Maria, Maria Dolores Velez, Carmen Diaz-Sala, Maria Teresa Cervera, Celia Maria Miguel
Summary: Recent studies have highlighted the increasing number of miRNAs and related sequences as critical mediators of environmental stress responses. Our comprehensive overview of the Pinus pinaster isomiRome reveals roots as the most responsive organ under drought conditions, with specific miRNA sequences showing significant down-regulation, including a novel 24nt miRNA. This study provides valuable insights for comparative studies between gymnosperms and angiosperms, and indicates high transferability of isomiRome between pine species for further molecular regulation and physiological studies related to drought adaptation.
PLANT CELL AND ENVIRONMENT
(2021)
Article
Oncology
Rosario Distefano, Giovanni Nigita, Patricia Le, Giulia Romano, Mario Acunzo, Patrick Nana-Sinkam
Summary: Post-transcriptional modifications in miRNA molecules have provided new insights into cancer biology and potential cancer biomarkers. In this study, we analyzed the profiles of canonical and non-canonical miRNAs in lung cancer patients of different races. We identified distinct post-transcriptional modifications in lung cancer tissues, indicating the relevance of miRNA isoforms as potential biomarkers. Concurrent profiling of canonical and non-canonical miRNAs may help identify additional biological pathways and biomarkers in lung cancer.
Review
Biochemical Research Methods
Georges Pierre Schmartz, Fabian Kern, Tobias Fehlmann, Viktoria Wagner, Bastian Fromm, Andreas Keller
Summary: With the rapid increase in RNA sequencing data sets, quantification and prediction of miRNAs, especially the analysis of isomiRs, have become major computational tasks. This study provides an overview of 27 computational solutions for isomiR analysis, categorizing and comparing tools to assist researchers in selecting the most suitable tool for their research tasks.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Anton Zhiyanov, Stepan Nersisyan, Alexander Tonevitsky
Summary: MiRNA isoforms (isomiRs) are single-stranded small RNAs produced from the same pri-miRNA hairpin through cleavage by Drosha and Dicer enzymes. Analysis of miRNA processing positions across 31 different cancers revealed that the positions are not tissue-specific and a model based on surrounding nucleotides can distinguish between homogeneous and heterogeneous cleavage. Additionally, some miRNAs show imprecise Dicer cleavage at the 5' end, while almost all cleavage sites at the 3' end are heterogeneous.
Article
Biochemical Research Methods
Ana M. Vasconcelos, Maria Beatriz Carmo, Beatriz Ferreira, Ines Viegas, Margarida Gama-Carvalho, Antonio Ferreira, Andreia J. Amaral
Summary: IsomiR Window is a platform developed to identify, quantify, and explore isomiR expression in small RNA-seq datasets. It includes a pipeline for data processing and a user-friendly interface, integrating various softwares for analysis and a new algorithm for detecting different types of isomiRs. The tool has been shown to accurately detect isomiRs with high confidence and has practical applications in studying miRNA variants in disease pathways.
BMC BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Li Guo, Dekang Ren, Yuting Zhang, Qiushi Wang, Shiyi Yu, Xinru Xu, Lulu Luo, Jiafeng Yu, Tingming Liang
Summary: MicroRNAs (miRNAs) are crucial regulators of gene expression and play important roles in various biological processes and tumorigenesis. Our comprehensive pan-cancer analysis reveals the potential relationships between multiple isomiRs and arm switching, and discusses their roles in tumorigenesis and cancer prognosis. Our findings suggest that different miR-#-5p and miR-#-3p pairs from the two arms of pre-miRNA have abundant expression levels and are involved in distinct functional regulatory networks, indicating their potential as prognostic biomarkers.
MOLECULAR GENETICS AND GENOMICS
(2023)
Article
Genetics & Heredity
Fu-Mei Hsieh, Su-Ting Lai, Ming-Fong Wu, Chen-Ching Lin
Summary: The research identified certain isomiRs in lung adenocarcinoma associated with better or poor prognosis. Protective isomiRs tend to be positively correlated and cooperate within the group, while harmful isomiRs show negative correlation and possible antagonistic effects between the protective and harmful groups. Two isomiRs of miR-181a-3p were found to belong to both harmful and protective groups, indicating a bidirectional regulation. Additionally, protective isomiRs of miR-21-5p may evolve as tumor suppressors by hindering metastasis.
FRONTIERS IN GENETICS
(2021)
Article
Biochemical Research Methods
Xavier Bofill-De Ros, Brian Luke, Robert Guthridge, Uma Mudunuri, Michael Loss, Shuo Gu
Summary: MicroRNAs (miRNAs) play a key role in regulating gene expression in cancers, with their sequence variants or isoforms (isomiRs) possessing unique functions. The Tumor IsomiR Encyclopedia (TIE) is a dynamic database that aggregates isomiR variants from over 10,000 tumor samples in TCGA and TARGET projects, addressing challenges in mapping isomiRs and overcoming the disregard of low frequency events. TIE's ability to annotate heterogeneous isomiR sequences and provide results for online browsing or download showcases its utility in analyzing miR-21 and miR-30a isomiRs.
Review
Biochemistry & Molecular Biology
Li Guo, Lin Jia, Lulu Luo, Xinru Xu, Yangyang Xiang, Yujie Ren, Dekang Ren, Lulu Shen, Tingming Liang
Summary: Circular RNAs (circRNAs) play a critical role in tumor metastasis by promoting tumor angiogenesis, regulating cellular functions, and interacting with the tumor microenvironment. Their potential clinical applications as biomarkers are promising.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Benchi Ma, Shihao Wang, Wenzheng Wu, Pufan Shan, Yufan Chen, Jiaqi Meng, Liping Xing, Jingyi Yun, Longhui Hao, Xiaoyu Wang, Shuyan Li, Yinghui Guo
Summary: In recent years, significant progress has been made in bioinformatics with the discovery of functional non-coding RNAs (ncRNAs). These ncRNAs play a crucial role in regulating intracellular gene expression, assisting in diagnosis, guiding drug use, and determining prognosis in various diseases. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are the three major types of ncRNAs that interact with each other. Studies have shown that lncRNAs and circRNAs can sponge miRNAs, influencing normal physiological processes and regulating mRNA expression, and ultimately affecting cellular physiology. This paper provides a summary of the mechanisms and research progress of these three ncRNAs and their potential implications in disease diagnosis, treatment, and drug development.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Kevin J. Peterson, Alan Beavan, Peter J. Chabot, Mark A. McPeek, Davide Pisani, Bastian Fromm, Oleg Simakov
Summary: WGDs do not result in the creation of miRNA novelty, nor do WGDs correlate to increases in complexity. Instead, it is the number of miRNA seed sequences in the genome itself that not only better correlate to instances in complexification, but also mechanistically explain why complexity increases when new miRNA families are established.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Review
Biochemistry & Molecular Biology
Scott Hotaling, Thomas Desvignes, John S. Sproul, Luana S. F. Lins, Joanna L. Kelley
Summary: This study utilized long-read sequencing data to generate a high-quality genome assembly for an Antarctic eelpout, Ophthalmolycus amberensis, and compared it to other Antarctic fishes. The study revealed unique evolution and adaptation features in O. amberensis and highlighted the importance of long-read sequencing in understanding genome evolution.
Article
Cardiac & Cardiovascular Systems
Florian Thibord, Derek Klarin, Jennifer A. Brody, Ming-Huei Chen, Michael G. Levin, Daniel Chasman, Ellen L. Goode, Kristian Hveem, Maris Teder-Laving, Angel Martinez-Perez, Dylan Aissi, Delphine Daian-Bacq, Kaoru Ito, Pradeep Natarajan, Pamela L. Lutsey, Girish N. Nadkarni, Paul S. de Vries, Gabriel Cuellar-Partida, Brooke N. Wolford, Jack W. Pattee, Charles Kooperberg, Sigrid K. Braekkan, Ruifang Li-Gao, Noemie Saut, Corriene Sept, Marine Germain, Renae L. Judy, Kerri L. Wiggins, Darae Ko, Christopher J. O'Donnell, Kent D. Taylor, Franco Giulianini, Mariza De Andrade, Therese H. Nost, Anne Boland, Jean-Philippe Empana, Satoshi Koyama, Thomas Gilliland, Ron Do, Jennifer E. Huffman, Xin Wang, Wei Zhou, Jose Manuel Soria, Juan Carlos Souto, Nathan Pankratz, Jeffery Haessler, Kristian Hindberg, Frits R. Rosendaal, Constance Turman, Robert Olaso, Rachel L. Kember, Traci M. Bartz, Julie A. Lynch, Susan R. Heckbert, Sebastian M. Armasu, Ben Brumpton, David M. Smadja, Xavier Jouven, Issei Komuro, Katharine R. Clapham, Ruth J. F. Loos, Cristen J. Willer, Maria Sabater-Lleal, James S. Pankow, Alexander P. Reiner, Vania M. Morelli, Paul M. Ridker, Astrid van Hylckama Vlieg, Jean-Francois Deleuze, Peter Kraft, Daniel J. Rader, Kyung Min Lee, Bruce M. Psaty, Anne Heidi Skogholt, Joseph Emmerich, Pierre Suchon, Stephen S. Rich, Ha My T. Vy, Weihong Tang, Rebecca D. Jackson, John-Bjarne Hansen, Pierre-Emmanuel Morange, Christopher Kabrhel, David-Alexandre Tregouet, Scott M. Damrauer, Andrew D. Johnson, Nicholas L. Smith
Summary: This study identified new genetic loci associated with VTE by using cross-ancestry genomic resources. The findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.
Article
Biochemistry & Molecular Biology
Ernesto Aparicio-Puerta, Pascal Hirsch, Georges P. Schmartz, Tobias Fehlmann, Verena Keller, Annika Engel, Fabian Kern, Michael Hackenberg, Andreas Keller
Summary: This article presents isomiRdb, a comprehensive resource that collects and organizes miRNA expression data at the isomiR resolution from various sources. It provides online access to millions of isomiR information and can be used to answer questions regarding the presence/absence of miRNA/isomiR in tissues.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Evolutionary Biology
Ana E. Jenike, Katharine M. Jenike, Kevin J. Peterson, Bastian Fromm, Marc K. Halushka
Summary: The evolution of specialized cell-types has long been a topic of interest for biologists, but it is difficult to reconstruct or observe due to deep time-scales. MicroRNAs have been found to be associated with the evolution of cellular complexity and may provide insights into specialization. This study focused on the evolutionary history of Mir-126, a microRNA specific to endothelial cells, to understand the origin of endothelium and its relationship with microRNA expression.
EVOLUTION & DEVELOPMENT
(2023)
Article
Cell Biology
Chantal Scheepbouwer, Ernesto Aparicio-Puerta, Cristina Gomez-Martin, Heleen Verschueren, Monique van Eijndhoven, Laurine E. Wedekind, Stavros Giannoukakos, Nathalie Hijmering, Lisa Gasparotto, Hilde T. van der Galien, Roos S. van Rijn, Eleonora Aronica, Robby Kibbelaar, Vivi M. Heine, Pieter Wesseling, David P. Noske, W. Peter Vandertop, Daphne de Jong, D. Michiel Pegtel, Michael Hackenberg, Tom Wurdinger, Alan Gerber, Danijela Koppers-Lalic
Summary: Transfer RNAs (tRNAs) play a vital role in mRNA translation, and changes in tRNA composition can directly impact cancer development and progression. To accurately assess tRNA expression and fragmentation levels, the ALL-tRNAseq technique was developed, which combines MarathonRT, RNA demethylation, and randomized adapter ligation prior to reverse transcription. This approach greatly improves the classification of oncogenic signatures in glioblastoma and diffuse large B-cell lymphoma tissues, particularly in samples with higher levels of RNA fragmentation.
GENES & DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Ernesto Aparicio-Puerta, Pascal Hirsch, Georges P. Schmartz, Fabian Kern, Tobias Fehlmann, Andreas Keller
Summary: miEAA is a flexible and comprehensive miRNA enrichment analysis tool based on direct and indirect miRNA annotation. It includes 19 miRNA repositories, covering 10 different organisms and 139,399 functional categories. miEAA has added information on the cellular context of miRNAs, isomiRs, and high-confidence miRNAs to improve the accuracy of results. It also improves the representation of aggregated results, including interactive Upset plots. Finally, miEAA demonstrates its functionality in the context of ageing and emphasizes the importance of carefully considering the miRNA input list. miEAA is free to use and publicly available.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Venetia Pliatsika, Tess Cherlin, Phillipe Loher, Panagiotis Vlantis, Parth Nagarkar, Stepan Nersisyan, Isidore Rigoutsos
Summary: MINRbase is a knowledge repository aimed at facilitating the study of ribosomal RNA-derived fragments (rRFs), providing interactive access to 130,238 expressed rRFs and allowing researchers to issue complex queries and explore detailed summaries of rRF expression and related features.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Fabian Kern, Thomas Kuhn, Nicole Ludwig, Martin Simon, Laura Groeger, Natalie Fabis, Ernesto Aparicio-Puerta, Abdulrahman Salhab, Tobias Fehlmann, Oliver Hahn, Annika Engel, Viktoria Wagner, Marcus Koch, Katarzyna Winek, Hermona Soreq, Irina Nazarenko, Gregor Fuhrmann, Tony Wyss-Coray, Eckart Meese, Verena Keller, Matthias W. Laschke, Andreas Keller
Summary: Previous studies have shown that RNA molecules exhibit global and tissue-specific ageing patterns in both murine models and humans. In this study, we focused on extracellular vesicles (EVs), which are membrane vesicles that mediate the transfer of genetic information between tissues. We sequenced small regulatory RNAs (sncRNAs) in two fractions of mouse plasma at different time points, and observed unique ageing patterns in different sncRNA classes between the free-circulating (fc-RNA) and EV-bound (EV-RNA) fractions. Furthermore, we found that miR-29 family in adipose tissues, particularly in the EV-RNA fraction, was strongly associated with ageing.
Editorial Material
Medicine, Research & Experimental
Xavier Bofill-De Ros
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Genetics & Heredity
Jessica N. Hatton, Megan N. Frone, Hannah C. Cox, Stephanie B. Crowley, Susan Hiraki, Noriko N. Yokoyama, Noura S. Abul-Husn, James F. Amatruda, Michael J. Anderson, Xavier Bofill-De Ros, Ann G. Carr, Elizabeth C. Chao, Kenneth S. Chen, Shuo Gu, Cecilia Higgs, Jerry Machado, Deborah Ritter, Kris Ann P. Schultz, Emily R. Soper, Mona K. Wu, Jessica L. Mester, Jung Kim, William D. Foulkes, Leora Witkowski, Douglas R. Stewart
Summary: Germline pathogenic variants in DICER1 predispose individuals to develop a variety of tumors, and accurate variant curation and classification are essential for diagnosis and surveillance. A DICER1-specific ACMG/AMP guideline was developed to improve objectivity and consistency in variant classification, resulting in successful classification of known pathogenic and benign variants.
Article
Hematology
Stepan Nersisyan, Emilie Montenont, Phillipe Loher, Elizabeth A. Middleton, Robert Campbell, Paul Bray, Isidore Rigoutsos
Summary: This study investigated the composition of sncRNAs in megakaryocytes (MKs) and platelets, as well as the impact of SARS-CoV-2 infection on platelet sncRNAs. The results showed that MKs primarily consist of isomiRs, tRFs, rRFs, and yRFs, while the platelets of healthy donors (HDs) are mainly composed of isomiRs. The sncRNA composition of platelets from COVID-19 patients differs significantly from that of HDs.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemical Research Methods
Monique A. J. van Eijndhoven, Chantal Scheepbouwer, Ernesto Aparicio-Puerta, Michael Hackenberg, D. Michiel Pegtel
Summary: This article presents IsoSeek, a sequencing protocol that improves the accuracy of miRNA detection in low input samples by reducing ligation and PCR amplification bias. The article provides detailed steps for using randomized adapters combined with unique molecular identifiers (UMI), library quantification, sequencing, and data processing and analysis.
Letter
Medicine, General & Internal
Bastian Fromm, Arun H. Patil, Marc K. Halushka
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Genetics & Heredity
Florian Thibord, Melissa Chan, Ming-Huei Chen, Andrew D. Johnson
Summary: Host genetic variants play a role in the susceptibility and severity of COVID-19. Research has identified genetic associations with COVID-19 that could aid in the development of new therapeutic strategies. Multiple genetic loci were found to be associated with COVID-19 susceptibility and severity, providing insights into the genetic mechanisms involved.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)