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Emerging role of long noncoding rnas in autoimmune diseases

AUTOIMMUNITY REVIEWS 2015年第9期14卷 798-805页

作者： Wu, Guo-Cui Pan, Hai-Feng Leng, Rui-Xue Wang, De-Guang Li, Xiang-Pei Li, Xiao-Mei Ye, Dong-Qing Anhui Med Univ Sch Publ Hlth Dept Epidemiol & Biostat Hefei 230032 Anhui Peoples R China Anhui Med Univ Anhui Prov Lab Populat Hlth & Major Dis Screening Hefei 230032 Anhui Peoples R China Anhui Med Univ Affiliated Hosp 2 Dept Nephrol Hefei 230601 Anhui Peoples R China Anhui Med Univ Anhui Prov Hosp Dept Rheumatol & Immunol Hefei 230001 Anhui Peoples R China

Long noncoding rna (lncrna), with size larger than 200 nucleotides, is a new class of noncoding rna. Emerging evidence has revealed that lncrnas play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncrna regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncrna regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncrnas in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD). (C) 2015 Elsevier B.V. All rights reserved.

关键词： lncrna noncoding rna Immune function Autoimmunity Autoimmune disease

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Predicting the Organelle Location of noncoding rnas Using Pseudo Nucleotide Compositions

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INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES 2017年第4期9卷 540-544页

作者： Feng, Pengmian Zhang, Jidong Tang, Hua Chen, Wei Lin, Hao North China Univ Sci & Technol Sch Publ Hlth Tangshan 063000 Peoples R China Zunyi Med Coll Dept Immunol Zunyi 563000 Peoples R China Sichuan Med Univ Dept Pathophysiol Luzhou 646000 Peoples R China North China Univ Sci & Technol Sch Sci Dept Phys Tangshan 063000 Peoples R China North China Univ Sci & Technol Ctr Genom & Computat Biol Tangshan 063000 Peoples R China Univ Elect Sci & Technol China Key Lab Neuroinformat Minist Educ Chengdu 610054 Sichuan Peoples R China Univ Elect Sci & Technol China Ctr Informat Biomed Sch Life Sci & Technol Chengdu 610054 Sichuan Peoples R China

noncoding rnas (ncrnas) are implicated in various biological processes. Recent findings have demonstrated that the function of ncrnas correlates with their provenance. Therefore, the recognition of ncrnas from different organelle genomes will be helpful to understand their molecular functions. However, the weakness of experimental techniques limits the progress toward studying organellar ncrnas and their functional relevance. As a complement of experiments, computational method provides an important choice to identify ncrna in different organelles. Thus, a computational model was developed to identify ncrnas from kinetoplast and mitochondrion organelle genomes. In this model, rna sequences are encoded by "pseudo dinucleotide composition." It was observed by the jackknife test that the overall success rate achieved by the proposed model was 90.08 %. We hope that the proposed method will be helpful in predicting ncrna organellar locations.

关键词： noncoding rna Organelle Support vector machine Pseudo nucleotide composition rna structural property

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Probing the function of long noncoding rnas in the nucleus

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CHROMOSOME RESEARCH 2020年第1期28卷 87-110页

作者： Akkipeddi, Sajal Medha K. Velleca, Anthony J. Carone, Dawn M. Swarthmore Coll Dept Biol Swarthmore PA 19081 USA Mem Sloan Kettering Canc Ctr Dept Mol Phamacol 1275 York Ave New York NY 10021 USA

The nucleus is a highly organized and dynamic environment where regulation and coordination of processes such as gene expression and DNA replication are paramount. In recent years, noncoding rnas have emerged as key participants in the regulation of nuclear processes. There are a multitude of functional roles for long noncoding rna (lncrna), mediated through their ability to act as molecular scaffolds bridging interactions with proteins, chromatin, and other rna molecules within the nuclear environment. In this review, we discuss the diversity of techniques that have been developed to probe the function of nuclear lncrnas, along with the ways in which those techniques have revealed insights into their mechanisms of action. Foundational observations into lncrna function have been gleaned from molecular cytology-based, single-cell approaches to illuminate both the localization and abundance of lncrnas in addition to their potential binding partners. Biochemical, extraction-based approaches have revealed the molecular contacts between lncrnas and other molecules within the nuclear environment and how those interactions may contribute to nuclear organization and regulation. Using examples of well-studied nuclear lncrnas, we demonstrate that the emerging functions of individual lncrnas have been most clearly deduced from combined cytology and biochemical approaches tailored to study specific lncrnas. As more functional nuclear lncrnas continue to emerge, the development of additional technologies to study their interactions and mechanisms of action promise to continually expand our understanding of nuclear organization, chromosome architecture, genome regulation, and disease states.

关键词： noncoding rna Nuclear organization Genome regulation Molecular cytology Microscopy Biochemical methods

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The Connection between the Growth Dynamics of Transplanted Lewis Carcinoma in Mice and Changes in the Activity of Genes and noncoding rnas after Low-Dose Irradiation

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BIOLOGY BULLETIN 2022年第12期49卷 2266-2278页

作者： Mikhailov, V. F. Saleeva, D. V. Shulenina, L. V. Raeva, N. F. Rozhdestvensky, L. M. Zasukhina, G. D. Fed Med Biol Agcy Burnasyan Fed Med Biophys Ctr Moscow Russia Russian Acad Sci Vavilov Inst Gen Genet Moscow Russia

The effect of low-dose radiation was studied on the growth dynamics of transfused Lewis carcinoma cells in female C57Bl/6 mice. Fourfold total fractionated irradiation was conducted at a dose of 75 mGy (at a dose rate of 0.154 Gy/min and a voltage of 200 kV), starting from day 10 after the transplantation with a four-day interval. On days 14 and 22, a group of mice was euthanized to study the expression levels of genes and noncoding rnas (micrornas and long noncoding rnas) in tumor cells, as well as in normal tissues (bone marrow, liver, spleen, thymus). The total rna was obtained, and complementary DNA was synthesized according to the manufacturer's protocol. After that, a real-time PCR reaction was performed using the SYBR Green I dye (Thermo Scientific, United States) or a TaqMan probe and specific primers. Genes and noncoding rnas were divided into groups of oncogenes and oncosuppressors according to scientific research. In the group of irradiated mice, a decrease in the tumor growth rate was observed, mainly from day 20, accompanied by a change in the activity of the studied genes. The ratio of the activity of oncosuppressors to oncogenes was calculated for the obtained tissues. These fractions were 0.5 for the tumor, 10.7 for the bone marrow, and 2.4 for the spleen and thymus. Thus, it can be stated that in the tumor there was a particularly pronounced activation of oncogenes compared to the activity of oncosuppressors, while the opposite effect was observed in normal tissues.

关键词： low-dose radiation Lewis lung carcinoma genes noncoding rna oncogenes oncosuppressors P53 NFkB

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Antisense long noncoding rnas regulate var gene activation in the malaria parasite Plasmodium falciparum

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2015年第9期112卷 E982-E991页

作者： Amit-Avraham, Inbar Pozner, Guy Eshar, Shiri Fastman, Yair Kolevzon, Netanel Yavin, Eylon Dzikowski, Ron Hebrew Univ Jerusalem Hadassah Med Sch Kuvin Ctr Study Infect & Trop Dis Inst Med Res Israel CanadaDept Microbiol & Mol G IL-91120 Jerusalem Israel Hebrew Univ Jerusalem Fac Med Sch Pharm Inst Drug Res IL-91120 Jerusalem Israel

The virulence of Plasmodium falciparum, the causative agent of the deadliest form of human malaria, is attributed to its ability to evade human immunity through antigenic variation. These parasites alternate between expression of variable antigens, encoded by members of a multicopy gene family named var. Immune evasion through antigenic variation depends on tight regulation of var gene expression, ensuring that only a single var gene is expressed at a time while the rest of the family is maintained transcriptionally silent. Understanding how a single gene is chosen for activation is critical for understanding mutually exclusive expression but remains a mystery. Here, we show that antisense long noncoding rnas (lncrnas) initiating from var introns are associated with the single active var gene at the time in the cell cycle when the single var upstream promoter is active. We demonstrate that these antisense transcripts are incorporated into chromatin, and that expression of these antisense lncrnas in trans triggers activation of a silent var gene in a sequence- and dose-dependent manner. On the other hand, interference with these lncrnas using complement peptide nucleic acid molecules down-regulated the active var gene, erased the epigenetic memory, and induced expression switching. Altogether, our data provide evidence that these antisense lncrnas play a key role in regulating var gene activation and mutually exclusive expression.

关键词： malaria Plasmodium falciparum var genes noncoding rna exclusive expression

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First Transcriptome Analysis of Hepatoblastoma in Brazil: Unraveling the Pivotal Role of noncoding rnas and Metabolic Pathways

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BIOCHEMICAL GENETICS 2024年 1-34页

作者： Aguiar, Talita Ferreira Marques Rivas, Maria Prates Silva, Edson Mario de Andrade Pires, Sara Ferreira Dangoni, Gustavo Dib Macedo, Taiany Curdulino Defelicibus, Alexandre Barros, Bruna Duraes de Figueiredo Novak, Estela Cristofani, Lilian Maria Odone, Vicente Cypriano, Monica de Toledo, Silvia Regina Caminada da Cunha, Isabela Werneck da Costa, Cecilia Maria Lima Carraro, Dirce Maria Tojal, Israel Mendes, Tiago Antonio de Oliveira Krepischi, Ana Cristina Victorino Univ Sao Paulo Inst Biosci Human Genome & Stem Cell Res Ctr Dept Genet & Evolutionary Biol So Paulo Brazil Columbia Univ Irving Med Ctr New York NY USA Univ Fed Vicosa Dept Biochem & Mol Biol Vicosa MG Brazil Int Ctr Res AC Camargo Canc Ctr So Paulo Brazil So Paulo Univ Pediat Canc Inst ITACI Med Sch Pediat Dept So Paulo Brazil Fed Univ So Paulo Dept Pediat Adolescent & Child Canc Support Grp GRAACC So Paulo Brazil Rede DOR So Luiz Rede OR Sao Luiz So Paulo Brazil Dept Pediat Oncol AC Camargo Canc Ctr So Paulo Brazil Univ Florida Hort Sci Dept Gainesville FL USA

Hepatoblastoma stands as the most prevalent liver cancer in the pediatric population. Characterized by a low mutational burden, chromosomal and epigenetic alterations are key drivers of its tumorigenesis. Transcriptome analysis is a powerful tool for unraveling the molecular intricacies of hepatoblastoma, shedding light on the effects of genetic and epigenetic changes on gene expression. In this study conducted in Brazilian patients, an in-depth whole transcriptome analysis was performed on 14 primary hepatoblastomas, compared to control liver tissues. The analysis unveiled 1,492 differentially expressed genes (1,031 upregulated and 461 downregulated), including 920 protein-coding genes (62%). Upregulated biological processes were linked to cell differentiation, signaling, morphogenesis, and development, involving known hepatoblastoma-associated genes (DLK1, MEG3, HDAC2, TET1, HMGA2, DKK1, DKK4), alongside with novel findings (GYNG4, CDH3, and TNFRSF19). Downregulated processes predominantly centered around oxidation and metabolism, affecting amines, nicotinamides, and lipids, featuring novel discoveries like the repression of SYT7, TTC36, THRSP, CCND1, GCK and CAMK2B. Two genes, which displayed a concordant pattern of DNA methylation alteration in their promoter regions and dysregulation in the transcriptome, were further validated by RT-qPCR: the upregulated TNFRSF19, a key gene in the embryonic development, and the repressed THRSP, connected to lipid metabolism. Furthermore, based on protein-protein interaction analysis, we identified genes holding central positions in the network, such as HDAC2, CCND1, GCK, and CAMK2B, among others, that emerged as prime candidates warranting functional validation in future studies. Notably, a significant dysregulation of non-coding rnas (ncrnas), predominantly upregulated transcripts, was observed, with 42% of the top 50 highly expressed genes being ncrnas. An integrative mirna-mrna analysis revealed crucial biological processe

关键词： Hepatoblastoma rna-seq Transcriptome noncoding rna Lipid Metabolism

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Analysis of autophagy-related genes and associated noncoding rnas and transcription factors in digestive system tumors

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FUTURE ONCOLOGY 2019年第36期15卷 4141-4154页

作者： Lin, Liewen Xia, Ligang Tang, Donge Dai, Yong Chen, Wenbiao Zhejiang Univ Affiliated Hosp 1 Collaborat Innovat Ctr Diag & Treatment Infect Di Coll MedNatl Clin Res Ctr Infect DisState Key L Hangzhou Zhejiang Peoples R China Southern Univ Sci & Technol Jinan Univ Shenzhen Peoples Hosp Clin Med Coll 2Affiliated Hosp 1Dept Clin Med R Shenzhen 518020 Guangdong Peoples R China Southern Univ Sci & Technol Affiliated Hosp 1 Jinan Univ Clin Med Coll 2Shenzhen Peoples HospDept Gastro Shenzhen 518020 Guangdong Peoples R China

Aim: To investigate the autophagy-related gene (ATG) expression and the associated noncoding rnas (ncrna) and transcription factors (TF) in digestive system tumors (DST). Methods: We systematically investigated the ATG expression in DST by weighted gene correlation network analysis, crosstalk connection, functional analysis and Pivot analysis. Results: ATGs were clustered into six modules with co-expression in DST. Functional analysis revealed that six ATG-related modules were enriched in biological pathways involved in tumorigenesis. Pivot analysis identified key ncrnas and TFs, which are essential for the pathogenesis, clinical diagnosis and treatment of DST. Conclusion: Our study highlights the crucial roles of ncrna and TFs in the identification of potential biomarkers or therapeutic targets for DST.

关键词： autophagy-related gene digestive system tumor noncoding rna pan-cancer transcription factor

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LncReader: identification of dual functional long noncoding rnas using a multi -head self-attention mechanism

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BRIEFINGS IN BIOINFORMATICS 2023年第1期24卷 bbac579-bbac579页

作者： Liu, Tianyuan Zou, Bohao He, Manman Hu, Yongfei Dou, Yiying Cui, Tianyu Tan, Puwen Li, Shaobin Rao, Shuan Huang, Yan Liu, Sixi Cai, Kaican Wang, Dong Southern Med Univ Guangzhou Peoples R China Univ Calif Davis Davis CA USA CAMS & Peking Union Med Coll Union NJ USA Southern Med Univ Nanfang Hosp Dept Thorac Surg Guangzhou Peoples R China Shenzhen Childrens Hosp Dept Hematol & Oncol Shenzhen Peoples R China Southern Med Univ Dept Bioinformat Guangzhou Peoples R China

Long noncoding ribonucleic acids (rnas;Lncrnas) endowed with both protein -coding and noncoding functions are referred to as 'dual functional lncrnas'. Recently, dual functional lncrnas have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell -type -specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncrnas. Here, we developed a deep -learning model with a multi -head self-attention mechanism, LncReader, to identify dual functional lncrnas. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncrnadb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with rna-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncrna identification.

关键词： noncoding rna system biology deep learning

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Identification of novel transcripts and noncoding rnas in bovine skin by deep next generation sequencing

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BMC GENOMICS 2013年第1期14卷 1-15页

作者： Weikard, Rosemarie Hadlich, Frieder Kuehn, Christa Leibniz Inst Farm Anim Biol FBN Inst Genome Biol D-18196 Dummerstorf Germany

Background: Deep rna sequencing (rnaseq) has opened a new horizon for understanding global gene expression. The functional annotation of non-model mammalian genomes including bovines is still poor compared to that of human and mouse. This particularly applies to tissues without direct significance for milk and meat production, like skin, in spite of its multifunctional relevance for the individual. Thus, applying an rnaseq approach, we performed a whole transcriptome analysis of pigmented and nonpigmented bovine skin to describe the comprehensive transcript catalogue of this tissue. Results: A total of 39,577 unique primary skin transcripts were mapped to the bovine reference genome assembly. The majority of the transcripts were mapped to known transcriptional units (65%). In addition to the reannotation of known genes, a substantial number (10,884) of unknown transcripts (UTs) were discovered, which had not previously been annotated. The classification of UTs was based on the prediction of their coding potential and comparative sequence analysis, subsequently followed by meticulous manual curation. The classification analysis and experimental validation of selected UTs confirmed that rnaseq data can be used to amend the annotation of known genes by providing evidence for additional exons, untranslated regions or splice variants, by approving genes predicted in silico and by identifying novel bovine loci. A large group of UTs (4,848) was predicted to potentially represent long noncoding rna (Incrna). Predominantly, potential Incrnas mapped in intergenic chromosome regions (4,365) and therefore, were classified as potential intergenic lncrna. Our analysis revealed that only about 6% of all UTs displayed interspecies conservation and discovered a variety of unknown transcripts without interspecies homology but specific expression in bovine skin. Conclusions: The results of our study demonstrate a complex transcript pattern for bovine skin and suggest a possible functi

关键词： Transcriptome rnaseq Skin Pigmentation noncoding rna Novel transcripts Cattle

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Creating conditional dual fluorescence labeled transgenic animals for studying function of small noncoding rnas

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CONNECTIVE TISSUE RESEARCH 2017年第1期58卷 103-115页

作者： Yang, Kun Gao, Yun Yang, Mingfu Xu, Zuoshang Chen, Qian Brown Univ Dept Orthoped Warren Alpert Med Sch 1 Hoppin St Providence RI 02903 USA Rhode Isl Hosp 1 Hoppin St Providence RI 02903 USA Univ Massachusetts Sch Med Dept Biochem & Mol Pharmacol Worcester MA USA

Because the function of most noncoding (nc) rnas is unknown, Cre-lox transgenic mice are useful tools to determine their functions in a tissue or developmental stage-specific manner. However, the technology faces challenges because expression of ncrna-transgene lacks protein product. No antibody or peptide-tag can be used to trace ncrna expression in mouse tissues in real time. Furthermore, transgene integration at different locus or orientations in the genome may result in recombination of genomic fragments in the Cre-lox system. Establishing a reliable method that can be used to determine the precise copy number and orientation of the transgene is critical to the field. We developed a fast and straightforward method to determine ncrna-transgene copy number, orientation, and insertion site in the genome. Furthermore, upon tissue-specific expression of ncrna, a Cre-loxP-mediated dual-fluorescence expression system facilitates fluorescence signal switching from green to red, which enables real-time monitoring of ncrna expression by fluorescence signals. As proof of concept, we demonstrate that after microrna (mirna)-Flox mice crossed with Col2a1-Cre mice, mirna transgene expression could be detected successfully by red fluorescence signals in various cartilaginous tissues. This method of creating small ncrna transgenic mice facilitates both tissue-specific ncrna expression and real-time visualization of its expression. It is particularly suitable for in vivo studies of the functional roles and lineage tracing of small ncrna.

关键词： Droplet digital PCR dual fluorescence switching system microrna noncoding rna transgene copy number transgenic mice

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