The Lncrna Toolkit: Databases and in Silico Tools for Lncrna Analysis
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Requirement of the Fusogenic Micropeptide Myomixer for Muscle Formation in Zebrafish
Requirement of the fusogenic micropeptide myomixer for muscle formation in zebrafish Jun Shia,b,1, Pengpeng Bia,b,c,1, Jimin Peid, Hui Lia,b,c, Nick V. Grishind,e, Rhonda Bassel-Dubya,b,c, Elizabeth H. Chena,b,2, and Eric N. Olsona,b,c,2 aDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390; bHamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; cSenator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; dHoward Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; and eDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390 Contributed by Eric N. Olson, September 28, 2017 (sent for review August 29, 2017; reviewed by Chen-Ming Fan and Thomas A. Rando) Skeletal muscle formation requires fusion of mononucleated myo- CRISPR/Cas9, we show that myomixer is required for zebrafish blasts to form multinucleated myofibers. The muscle-specific mem- myoblast fusion. We also identify additional distantly related brane proteins myomaker and myomixer cooperate to drive myomixer orthologs from genomes of turtle and elephant shark, mammalian myoblast fusion. Whereas myomaker is highly conserved which like zebrafish myomixer can substitute for mouse myomixer across diverse vertebrate species, myomixer is a micropeptide that to promote cell fusion together with myomaker in cultured cells. shows relatively weak cross-species conservation. To explore the By comparison of amino acid sequences across these diverse functional conservation of myomixer, we investigated the expres- species, we identify a unique protein motif required for the sion and function of the zebrafish myomixer ortholog. -
Computational Analysis Predicts Hundreds of Coding Lncrnas in Zebrafish
biology Communication Computational Analysis Predicts Hundreds of Coding lncRNAs in Zebrafish Shital Kumar Mishra 1,2 and Han Wang 1,2,* 1 Center for Circadian Clocks, Soochow University, Suzhou 215123, China; [email protected] 2 School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China * Correspondence: [email protected] or [email protected]; Tel.: +86-512-6588-2115 Simple Summary: Noncoding RNAs (ncRNAs) regulate a variety of fundamental life processes such as development, physiology, metabolism and circadian rhythmicity. RNA-sequencing (RNA- seq) technology has facilitated the sequencing of the whole transcriptome, thereby capturing and quantifying the dynamism of transcriptome-wide RNA expression profiles. However, much remains unrevealed in the huge noncoding RNA datasets that require further bioinformatic analysis. In this study, we applied six bioinformatic tools to investigate coding potentials of approximately 21,000 lncRNAs. A total of 313 lncRNAs are predicted to be coded by all the six tools. Our findings provide insights into the regulatory roles of lncRNAs and set the stage for the functional investigation of these lncRNAs and their encoded micropeptides. Abstract: Recent studies have demonstrated that numerous long noncoding RNAs (ncRNAs having more than 200 nucleotide base pairs (lncRNAs)) actually encode functional micropeptides, which likely represents the next regulatory biology frontier. Thus, identification of coding lncRNAs from ever-increasing lncRNA databases would be a bioinformatic challenge. Here we employed the Coding Potential Alignment Tool (CPAT), Coding Potential Calculator 2 (CPC2), LGC web server, Citation: Mishra, S.K.; Wang, H. Coding-Non-Coding Identifying Tool (CNIT), RNAsamba, and MicroPeptide identification tool Computational Analysis Predicts (MiPepid) to analyze approximately 21,000 zebrafish lncRNAs and computationally to identify Hundreds of Coding lncRNAs in 2730–6676 zebrafish lncRNAs with high coding potentials, including 313 coding lncRNAs predicted Zebrafish. -
Stem Cell Metabolic and Epigenetic Reprogramming
RESEARCH HIGHLIGHTS Cell 16, 39–50, 2015). They discovered that inactivating Rb facilitates Enhancer evolution in mammals reprogramming of fibroblasts to a pluripotent state. Surprisingly, their Widespread changes in regulatory genomic regions have data indicate that this does not involve interference with the cell cycle but underpinned mammalian evolution, but our knowledge about instead that Rb directly binds to and represses pluripotency-associated these regions is still incomplete. Paul Flicek, Duncan Odom and loci such as Oct4 (Pou5f1) and Sox2. Loss of Rb seems to compensate colleagues have now contributed to a better understanding of for the omission of Sox2 from the cocktail of reprogramming factors. how the noncoding portions of mammalian genomes have been Furthermore, genetic disruption of Sox2 precludes tumor formation in reshaped over the last 180 million years (Cell 160, 554–566, mice lacking functional Rb protein. This study positions Rb as a repres- 2015). They characterized active promoters and enhancers in sor of the pluripotency gene regulatory network and suggests that loss of liver samples from 20 mammalian species—from Tasmanian Rb might clear the path for Sox2, or other master regulators of stem cell devil to human—by examining the genome-wide enrichment identity, to induce cancer. It will be interesting to analyze the potential profiles of H3K4me3 and H3K27ac, two histone modifications role of Rb in other types of in vitro reprogramming. TF associated with transcriptional activity. Their analyses suggest that rapid enhancer evolution and high promoter conservation are fundamental traits of mammalian genomes. Intriguingly, they Micropeptide regulates muscle performance find that the majority of newly evolved enhancers originated via It is becoming increasingly recognized that some transcripts anno- functional exaptation of ancestral DNA and not through clade- tated as long noncoding RNAs (lncRNAs) contain short ORFs that specific expansions of repeat elements. -
Lncrna GAS5 Overexpression Downregulates IL-18 and Induces the Apoptosis of Fibroblast-Like Synoviocytes
Clinical Rheumatology (2019) 38:3275–3280 https://doi.org/10.1007/s10067-019-04691-2 ORIGINAL ARTICLE LncRNA GAS5 overexpression downregulates IL-18 and induces the apoptosis of fibroblast-like synoviocytes Cuili Ma1 & Weigang Wang2 & Ping Li 1 Received: 19 March 2019 /Revised: 26 June 2019 /Accepted: 10 July 2019 /Published online: 1 August 2019 # International League of Associations for Rheumatology (ILAR) 2019 Abstract Background Long non-coding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) negatively regulates interleukin-18 (IL-18) in ovarian cancer, while IL-18 contributes to the development of rheumatoid arthritis (RA). Therefore, GAS5 may also participate in RA. Methods GAS5 and IL-18 in plasma of RA patients (n = 60) and healthy controls (n = 60) were measured by RT-qPCR and ELISA, respectively. Linear regression was performed to analyze the correlations between plasma levels of IL-18 and GAS5 in both RA patients and healthy controls. Results In the present study, we found that plasma GAS5 was downregulated, while IL-18 was upregulated in RA patients than in healthy controls. A significant and inverse correlation between GAS5 and IL-18 was found in RA patients but not in healthy controls. IL-18 treatment did not significantly alter the expression of GAS5 in fibroblast-like synoviocytes, while GAS5 overexpression led to the inhibited expression of IL-18. GAS5 overexpression also resulted in the promoted apoptosis of fibroblast-like synoviocytes. Conclusions Therefore, GAS5 overexpression may improve RA by downregulating IL-18 and inducing the apoptosis of fibroblast-like synoviocytes. Key points • The present study mainly showed that overexpression of GAS5 may assist the treatment of RA. -
Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: a Translational Study in Pediatric Patients with IBD
International Journal of Molecular Sciences Article Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD Marianna Lucafò 1 , Letizia Pugnetti 2, Matteo Bramuzzo 1 , Debora Curci 2, Alessia Di Silvestre 2, Annalisa Marcuzzi 1 , Alberta Bergamo 3, Stefano Martelossi 4, Vincenzo Villanacci 5, Anna Bozzola 5, Moris Cadei 5, Sara De Iudicibus 1, Giuliana Decorti 1,6,* and Gabriele Stocco 7 1 Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, 34137 Trieste, Italy; [email protected] (M.L.); [email protected] (M.B.); [email protected] (A.M.); [email protected] (S.D.I.) 2 PhD School in Science of Reproduction and Development, University of Trieste, 34127 Trieste, Italy; [email protected] (L.P.); [email protected] (D.C.); [email protected] (A.D.S.) 3 Callerio Foundation Onlus, 34127 Trieste, Italy; [email protected] 4 Cà Foncello Hospital, 31100 Treviso, Italy; [email protected] 5 Pathology Section, Spedali Civili, 25123 Brescia, Italy; [email protected] (V.V.); [email protected] (A.B.); [email protected] (M.C.) 6 Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy 7 Department of Life Sciences, University of Trieste, 34127 Trieste, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-04-0558-8634 !"#!$%&'(! Received: 24 September 2019; Accepted: 21 October 2019; Published: 24 October 2019 !"#$%&' Abstract: Background: The long non-coding RNA (lncRNA) growth arrest–specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). -
GAS5) Protects Ovarian Cancer Cells from Apoptosis
Int J Clin Exp Pathol 2016;9(9):9028-9037 www.ijcep.com /ISSN:1936-2625/IJCEP0028395 Original Article Long non-coding RNA growth arrest-specific transcript 5 (GAS5) protects ovarian cancer cells from apoptosis Jiayin Gao1, Beidi Wang1, Min Mao2, Song Zhang3, Meiling Sun4, Peiling Li1 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; 2Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, China; 3Department of Medical Service, The First Affiliated Hospital of Harbin Medical University, Harbin, China; 4Department of Nursing, The Second Affiliated Hospital of Harbin Medical University, Harbin, China Received March 16, 2016; Accepted July 12, 2016; Epub September 1, 2016; Published September 15, 2016 Abstract: Epithelial ovarian cancer (EOC) is a main cause of death in malignant tumor of women genital system. This study aims to investigate the underlying role of growth arrest-specific transcript 5 (GAS5) in EOC. In vivo expression of GAS5 in 60 EOC specimens was evaluated by quantitative reverse transcription QRT-PCR, which used to study the differences of GAS5 expression between EOC tissues and normal ovarian epithelium. There were no significant differences of GAS5 expression between normal ovarian epithelium and benign epithelial lesions; however, GAS5 expression was lower in EOC tissues compared with normal ovarian epithelial tissues (6.44-fold), which was closely related to lymph node metastasis (P=0.025) and tumor node metastasis stage (P=0.035). Moreover, exogenous GAS5-inhibited proliferation promoted apoptosis and decreased migration and invasion in ovarian cancer cells. Finally, through Western blot analysis, overexpression of GAS5 protein could decrease the expression of Cyclin A, Cyclin D, Cyclin E, and PCNA. -
Minireview: Novel Micropeptide Discovery by Proteomics and Deep Sequencing Methods
fgene-12-651485 May 6, 2021 Time: 11:28 # 1 MINI REVIEW published: 06 May 2021 doi: 10.3389/fgene.2021.651485 Minireview: Novel Micropeptide Discovery by Proteomics and Deep Sequencing Methods Ravi Tharakan1* and Akira Sawa2,3 1 National Institute on Aging, National Institutes of Health, Baltimore, MD, United States, 2 Departments of Psychiatry, Neuroscience, Biomedical Engineering, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3 Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States A novel class of small proteins, called micropeptides, has recently been discovered in the genome. These proteins, which have been found to play important roles in many physiological and cellular systems, are shorter than 100 amino acids and were overlooked during previous genome annotations. Discovery and characterization of more micropeptides has been ongoing, often using -omics methods such as proteomics, RNA sequencing, and ribosome profiling. In this review, we survey the recent advances in the micropeptides field and describe the methodological and Edited by: conceptual challenges facing future micropeptide endeavors. Liangliang Sun, Keywords: micropeptides, miniproteins, proteogenomics, sORF, ribosome profiling, proteomics, genomics, RNA Michigan State University, sequencing United States Reviewed by: Yanbao Yu, INTRODUCTION J. Craig Venter Institute (Rockville), United States The sequencing and publication of complete genomic sequences of many organisms have aided Hongqiang Qin, the medical sciences greatly, allowing advances in both human genetics and the biology of human Dalian Institute of Chemical Physics, Chinese Academy of Sciences, China disease, as well as a greater understanding of the biology of human pathogens (Firth and Lipkin, 2013). -
A Report on Box C/D Small Nucleolar RNA Editing in Human Cells
ORIGINAL RESEARCH published: 04 November 2019 doi: 10.3389/fphar.2019.01246 Are Small Nucleolar RNAs “CRISPRable”? A Report on Box C/D Small Nucleolar RNA Editing in Human Cells Julia A. Filippova 1†, Anastasiya M. Matveeva 1,2†, Evgenii S. Zhuravlev 1, Evgenia A. Balakhonova 1, Daria V. Prokhorova 1,2, Sergey J. Malanin 3, Raihan Shah Mahmud 3, Tatiana V. Grigoryeva 3, Ksenia S. Anufrieva 4,5, Dmitry V. Semenov 1, Valentin V. Vlassov 1 and Grigory A. Stepanov 1,2* Edited by: Hector A. Cabrera-Fuentes, 1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, University of Giessen, Germany Russia, 2 Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia, 3 Institute of Fundamental Reviewed by: Medicine and Biology, Kazan Federal University, Kazan, Russia, 4 Department of Biological and Medical Physics, Moscow Stephanie Kehr, Institute of Physics and Technology (State University), Moscow, Russia, 5 Laboratory of Cell Biology, Federal Research and University Hospital Leipzig, Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, Moscow, Russia Germany Christopher Holley, Duke University, United States CRISPR technologies are nowadays widely used for targeted knockout of numerous *Correspondence: protein-coding genes and for the study of various processes and metabolic pathways in Grigory A. Stepanov human cells. Most attention in the genome editing field is now focused on the cleavage [email protected] of protein-coding genes or genes encoding long non-coding RNAs (lncRNAs), while †These authors have contributed the studies on targeted knockout of intron-encoded regulatory RNAs are sparse. -
The Long Non-Coding RNA Meg3 Is Dispensable for Hematopoietic Stem Cells
www.nature.com/scientificreports OPEN The long non-coding RNA Meg3 is dispensable for hematopoietic stem cells Received: 10 October 2018 Pia Sommerkamp1,2,3, Simon Renders1,2, Luisa Ladel1,2, Agnes Hotz-Wagenblatt 4, Accepted: 2 January 2019 Katharina Schönberger1,2,5, Petra Zeisberger1,2, Adriana Przybylla1,2, Markus Sohn1,2, Published: xx xx xxxx Yunli Zhou6, Anne Klibanski6, Nina Cabezas-Wallscheid1,2,5 & Andreas Trumpp1,2 The long non-coding RNA (lncRNA) Maternally Expressed Gene 3 (Meg3) is encoded within the imprinted Dlk1-Meg3 gene locus and is only maternally expressed. Meg3 has been shown to play an important role in the regulation of cellular proliferation and functions as a tumor suppressor in numerous tissues. Meg3 is highly expressed in mouse adult hematopoietic stem cells (HSCs) and strongly down-regulated in early progenitors. To address its functional role in HSCs, we used MxCre to conditionally delete Meg3 in the adult bone marrow of Meg3mat-fox/pat-wt mice. We performed extensive in vitro and in vivo analyses of mice carrying a Meg3 defcient blood system, but neither observed impaired hematopoiesis during homeostatic conditions nor upon serial transplantation. Furthermore, we analyzed VavCre Meg3mat-fox/pat-wt mice, in which Meg3 was deleted in the embryonic hematopoietic system and unexpectedly this did neither generate any hematopoietic defects. In response to interferon-mediated stimulation, Meg3 defcient adult HSCs responded highly similar compared to controls. Taken together, we report the fnding, that the highly expressed imprinted lncRNA Meg3 is dispensable for the function of HSCs during homeostasis and in response to stress mediators as well as for serial reconstitution of the blood system in vivo. -
Regulation of Apoptosis by Long Non-Coding RNA GAS5 in Breast Cancer Cells: 1 2 Implications for Chemotherapy 3 4 5 6 7 8 9 Mark R
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by ChesterRep Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: 1 2 implications for chemotherapy 3 4 5 6 7 8 9 Mark R. Pickard* & Gwyn T. Williams* 10 11 12 Apoptosis Research Group, Institute of Science and Technology in Medicine, Huxley 13 14 15 Building, School of Life Sciences, Keele University, Keele ST5 5BG, United Kingdom. 16 17 18 19 20 21 22 23 24 25 *Corresponding authors: 26 27 28 M.R.Pickard: E-mail: [email protected]; Tel: 0044 (0)1782 733671; Fax: 0044 29 30 (0)1782 733516 31 32 33 34 G.T. Williams: E-mail: [email protected]; Tel: 0044 (0)1782 733032; Fax: 0044 35 36 (0)1782 733516 37 38 39 40 41 42 43 Running title: GAS5 and breast cancer 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 1 63 64 65 1 2 Abstract 3 4 5 Purpose: The putative tumour suppressor and apoptosis-promoting gene, growth arrest- 6 7 8 specific 5 (GAS5), encodes lncRNA and snoRNAs. Its expression is down-regulated in breast 9 10 cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences 11 12 13 of decreased GAS5 expression for breast cancer cell survival following treatment with 14 15 chemotherapeutic agents are addressed. In addition, functional responses of triple-negative 16 17 18 breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to 19 20 enhance cellular GAS5 levels is investigated. -
Dysfunction of the WT1-MEG3 Signaling Promotes AML Leukemogenesis Via P53-Dependent and -Independent Pathways
OPEN Leukemia (2017) 31, 2543–2551 www.nature.com/leu ORIGINAL ARTICLE Dysfunction of the WT1-MEG3 signaling promotes AML leukemogenesis via p53-dependent and -independent pathways YLyu1,2,7, J Lou1,3,7, Y Yang1,2,7, J Feng1,7, Y Hao1, S Huang1, L Yin1,2,JXu1, D Huang1,2,BMa1,3, D Zou1, Y Wang1,2, Y Zhang1, B Zhang3, P Chen4,KYu5, EW-F Lam6, X Wang1, Q Liu1,JYan1,2 and B Jin1 Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA maternally expressed gene 3 (MEG3) inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly downregulated in AML and suppresses leukemogenesis not only in a p53-dependent, but also a p53-independent manner. In addition, MEG3 is proven to be transcriptionally activated by Wilms’ tumor 1 (WT1), dysregulation of which by epigenetic silencing or mutations is causally involved in AML. Therefore MEG3 is identified as a novel target of the WT1 molecule. Ten–eleven translocation-2 (TET2) mutations frequently occur in AML and significantly promote leukemogenesis of this disorder. In our study, TET2, acting as a cofactor of WT1, increases MEG3 expression. Taken together, our work demonstrates that TET2 dysregulated WT1-MEG3 axis significantly promotes AML leukemogenesis, paving a new avenue for diagnosis and treatment of AML patients. -
Micropeptide Regulates Muscle Performance
RESEARCH HIGHLIGHTS Cell 16, 39–50, 2015). They discovered that inactivating Rb facilitates Enhancer evolution in mammals reprogramming of fibroblasts to a pluripotent state. Surprisingly, their Widespread changes in regulatory genomic regions have data indicate that this does not involve interference with the cell cycle but underpinned mammalian evolution, but our knowledge about instead that Rb directly binds to and represses pluripotency-associated these regions is still incomplete. Paul Flicek, Duncan Odom and loci such as Oct4 (Pou5f1) and Sox2. Loss of Rb seems to compensate colleagues have now contributed to a better understanding of for the omission of Sox2 from the cocktail of reprogramming factors. how the noncoding portions of mammalian genomes have been Furthermore, genetic disruption of Sox2 precludes tumor formation in reshaped over the last 180 million years (Cell 160, 554–566, mice lacking functional Rb protein. This study positions Rb as a repres- 2015). They characterized active promoters and enhancers in sor of the pluripotency gene regulatory network and suggests that loss of liver samples from 20 mammalian species—from Tasmanian Rb might clear the path for Sox2, or other master regulators of stem cell devil to human—by examining the genome-wide enrichment identity, to induce cancer. It will be interesting to analyze the potential profiles of H3K4me3 and H3K27ac, two histone modifications role of Rb in other types of in vitro reprogramming. TF associated with transcriptional activity. Their analyses suggest that rapid enhancer evolution and high promoter conservation are fundamental traits of mammalian genomes. Intriguingly, they Micropeptide regulates muscle performance find that the majority of newly evolved enhancers originated via It is becoming increasingly recognized that some transcripts anno- functional exaptation of ancestral DNA and not through clade- tated as long noncoding RNAs (lncRNAs) contain short ORFs that specific expansions of repeat elements.