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rna-directed DNA methylation requires stepwise binding of silencing factors to long non-coding rna

PLANT JOUrnaL 2014年第2期79卷 181-191页

作者： Boehmdorfer, Gudrun Rowley, M. Jordan Kucinski, Jan Zhu, Yongyou Amies, Ivan Wierzbicki, Andrzej T. Univ Michigan Dept Mol Cellular & Dev Biol Ann Arbor MI 48109 USA

Ribonucleic acid-mediated transcriptional gene silencing (known as rna-directed DNA methylation, or RdDM, in Arabidopsis thaliana) is important for influencing gene expression and the inhibition of transposons by the deposition of repressive chromatin marks such as histone modifications and DNA methylation. A key event in de novo methylation of DNA by RdDM is the production of long non-coding rna (lncrna) by rna polymerase V (Pol V). Little is known about the events that connect Pol V transcription to the establishment of repressive chromatin modifications. Using rna immunoprecipitation, we elucidated the order of events downstream of lncrna production and discovered interdependency between lncrna-associated proteins. We found that the effector protein ARGONAUTE4 (AGO4) binds lncrna independent of the rna-binding protein INVOLVED IN DE NOVO2 (IDN2). In contrast, IDN2 binds lncrna in an AGO4-dependent manner. We further found that the de novo DNA methyltransferase DOMAINS REARRANGED METHYL-TRANSFERASE2 (DRM2) also associates with lncrna produced by Pol V and that this event depends on AGO4 and IDN2. We propose a model where the silencing proteins AGO4, IDN2 and DRM2 bind to lncrna in a stepwise manner, resulting in DNA methylation of RdDM target loci.

关键词： non-coding rna DNA methyltransferase Argonaute INVOLVED IN DE NOVO2 Arabidopsis thaliana

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Recent advances in exosomal non-coding rna-based therapeutic approaches for photoaging

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SKIN RESEARCH AND TECHNOLOGY 2023年第9期29卷 e13463页

作者： Li, Kun-Jie Zhou, Peng-Jun Guo, Yan-Ni Xu, Tian-Xing Lin, Song-Fa Lin, Shu Ji, Chao Fujian Med Univ Affiliated Hosp 2 Dept Dermatol Quanzhou Fujian Peoples R China Fujian Med Univ Affiliated Hosp 2 Ctr Neurol & Metab Res Quanzhou Fujian Peoples R China Garvan Inst Med Res Grp Neuroendocrinol Sydney Australia Fujian Med Univ Affiliated Hosp 1 Dept Dermatol Fuzhou Fujian Peoples R China Garvan Inst Med Res Grp Neuroendocrinol 384 Victoria St Sydney NSW 2010 Australia Fujian Med Univ Affiliated Hosp 1 Dept Dermatol 20 Chazhong Rd Fuzhou Fujian Peoples R China

BackgroundPhotoaging is a degenerative biological process that affects the quality of life. It is caused by environmental factors including ultraviolet radiation (UVR), deep skin burns, smoking, active oxygen, chemical substances, and trauma. Among them, UVR plays a vital role in the aging *** the continuous development of modern medicine, clinical researchers have investigated novel approaches to treat aging. In particular, mesenchymal stem cells (MSCs), non-coding rnas are involved in various physiological processes have broad clinical application as they have the advantages of convenient samples, abundant sources, and avoidable ethical *** article reviews research progress on five types of stem cell, exosomes, non-coding rna in the context of photoaging treatment: adipose-derived stem cell, human umbilical cord MSCs, epidermal progenitor cells, keratinocyte stem cells, and hair follicle stem cells (HFSCs). It also includes stem cell related exosomes and their non-coding rna *** results have clinical guiding significance for prevention and control of the onset and development of photoaging. It is found that stem cells secrete cytokines, cell growth factors, non-coding rna, exosomes and proteins to repair aging skin tissues and achieve skin rejuvenation. In particular, stem cell exosomes and non-coding rna are found to have significant research potential, as they possess the benefits of their source cells without the disadvantages which include immune rejection and granuloma formation.

关键词： exosome mesenchymal stem cells non-coding rna photoaging skin cancer ultraviolet radiation

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ncRDeep: non-coding rna classification with convolutional neural network

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COMPUTATIONAL BIOLOGY AND CHEMISTRY 2020年 88卷 107364页

作者： Chantsalnyam, Tuvshinbayar Lim, Dae Yeong Tayara, Hilal Chong, Kil To Jeonbuk Natl Univ Dept Elect & Informat Engn Jeonju 54896 South Korea Jeonbuk Natl Univ Adv Elect & Informat Res Ctr Jeonju 54896 South Korea

A non-coding rna (ncrna) is a kind of rna that is not converted into protein, however, it is involved in many biological processes, diseases, and cancers. Numerous ncrnas have been identified and classified with high throughput sequencing technology. Hence, accurate ncrnas class prediction is important and necessary for further study of their functions. Several computation techniques have been employed to predict the class of ncrnas. Recent classification methods used the secondary structure as their primary input. However, the computational tools of rna secondary structure are not accurate enough which affects the final performance of ncrnas predictors. In this paper, we propose a simple yet efficient method, called ncRDeep, for ncrnas pre-diction. It uses a simple convolutional neural network and rna sequence information only. The ncRDeep was evaluated on benchmark datasets and the comparison results showed that the ncRDeep outperforms the state-ofthe-art methods significantly. More specifically, the average accuracy was improved by 8.32%.

关键词： Convolution neural network Classification Deep learning non-coding rna

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Comparison and benchmark of deep learning methods for non-coding rna classification

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PLOS COMPUTATIONAL BIOLOGY 2024年第9期20卷 e1012446页

作者： Creux, Constance Zehraoui, Farida Radvanyi, Francois Tahi, Fariza Univ Evry Univ Paris Saclay IBISC Evry Courcouronnes France PSL Res Univ Inst Curie Mol Oncol CNRSUMR Paris France

The involvement of non-coding rnas in biological processes and diseases has made the exploration of their functions crucial. Most non-coding rnas have yet to be studied, creating the need for methods that can rapidly classify large sets of non-coding rnas into functional groups, or classes. In recent years, the success of deep learning in various domains led to its application to non-coding rna classification. Multiple novel architectures have been developed, but these advancements are not covered by current literature reviews. We present an exhaustive comparison of the different methods proposed in the state-of-the-art and describe their associated datasets. Moreover, the literature lacks objective benchmarks. We perform experiments to fairly evaluate the performance of various tools for non-coding rna classification on popular datasets. The robustness of methods to non-functional sequences and sequence boundary noise is explored. We also measure computation time and CO2 emissions. With regard to these results, we assess the relevance of the different architectural choices and provide recommendations to consider in future methods. rna can either encode proteins, which perform different functions in the genome, or be non-coding. non-coding rnas represent around 98% of the genome, and were long thought to be non-functional. It has now been proven that non-coding rnas can have diverse biological functions and be involved in diseases. A large proportion of non-coding rnas has not yet been studied. The function of specific non-coding rnas can be studied experimentally, but experiments are costly and time-consuming. One possibility to massively characterize the function of non-coding rnas is to use computational methods to classify them into functional groups, or classes. Recent computational methods for non-coding rna classification are all based on deep learning, as it leads to faster runtime and improved performance. Our work presents and compares the different approa

关键词： non-coding rna Source code Carbon dioxide rna structure Nucleotide sequencing Epigenetics Deep learning Micrornas

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Long Intergenic non-coding rna LINC00885 Promotes Tumorigenesis of Cervical Cancer by Upregulating MACC1 Expression Through Serving as a Competitive Endogenous rna for microrna-432-5p

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Cancer Management and Research 2021年 13卷 1435-1447页

作者： Hongwei Chen Yugang Chi Mengyue Chen Limei Zhao 1 Department of Gynaecology The First People’s Hospital of Chongqing Liangjiang New Area Chongqing 401120 People’s Republic of China 2 Department of Gynaecology and Obstetrics Chongqing Health Center for Women and Children Chongqing 400021 People’s Republic of China

PurposeLong intergenic non-protein coding rna 885 (LINC00885) has been well studied in breast cancer; however, its contribution in cervical cancer remains unclear. In this study, we aimed to determine the detailed functions of LINC00885 in cervical cancer and elucidate the underlying molecular regulation *** expression status of LINC00885 in cervical cancer was determined using reverse transcription-quantitative polymerase chain reaction and by searching The Cancer Genome Atlas database. The detailed functions of LINC00885 in cervical cancer cells were confirmed using Cell Counting Kit 8 assay, flow cytometry analysis, Transwell cell migration and invasion assays, and tumor xenograft assay. Mechanistic experiments included bioinformatics prediction, rna immunoprecipitation, luciferase reporter assay, and rescue ***00885 was clearly overexpressed in cervical cancer, which was linked with unfavorable clinical outcomes. Functionally, LINC00885 deficiency suppressed cervical cancer cell proliferation, migration, and invasion but stimulated cell apoptosis in vitro. Furthermore, loss of LINC00885 restricted the growth of cervical cancer cells in vivo. Mechanistically, LINC00885 functioned as a competitive endogenous rna for microrna-432-5p (miR-432-5p) in cervical cancer. Furthermore, metastasis-associated colon cancer 1 (MACC1) was confirmed as the direct target of miR-432-5p, and LINC00885 could enhance MACC1 expression by sequestering miR-432-5p. Rescue experiments revealed that silencing of miR-432-5p or upregulation of MACC1 expression could effectively counteract the restrained aggressive properties of cervical cancer cells induced by LINC00885 ***00885 upregulated MACC1 expression in cervical cancer cells by sponging miR-432-5p, thereby promoting cancer progression. The LINC00885/miR-432-5p/MACC1 pathway may help in the identification of potential prognostic biomarkers and therapeutic targets in cervical ca

关键词： non-coding rna competitive endogenous rna LINC00885 microrna-432-5p cervical cancer MACC1

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non-coding rna Analysis Using the Rfam Database

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Current Protocols in Bioinformatics 2018年第1期62卷 e51页

作者： Kalvari, Ioanna Nawrocki, Eric P. Argasinska, Joanna Quinones-Olvera, Natalia Finn, Robert D. Bateman, Alex Petrov, Anton I. European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge United Kingdom National Center for Biotechnology Information National Institutes of Health Department of Health and Human Services Bethesda MD United States Systems Biology Graduate Program Harvard University Cambridge MA United States

Rfam is a database of non-coding rna families in which each family is represented by a multiple sequence alignment, a consensus secondary structure, and a covariance model. Using a combination of manual and literature-based curation and a custom software pipeline, Rfam converts descriptions of rna families found in the scientific literature into computational models that can be used to annotate rnas belonging to those families in any DNA or rna sequence. Valuable research outputs that are often locked up in figures and supplementary information files are encapsulated in Rfam entries and made accessible through the Rfam Web site. The data produced by Rfam have a broad application, from genome annotation to providing training sets for algorithm development. This article gives an overview of how to search and navigate the Rfam Web site, and how to annotate sequences with rna families. The Rfam database is freely available at http://***. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

关键词： genome annotation Infernal non-coding rna Rfam rna family

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RETRACTED ARTICLE: Long non-coding rna DARS-AS1 Contributes to Prostate Cancer Progression Through Regulating the Microrna-628-5p/MTDH Axis

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Cancer Management and Research 2020年 12卷 8363-8377页

作者： Haitao Fan Junhui Hou Siqing Liu Zuomin Xiao Jia Cui 1 Department of Urology The Second Hospital of Jilin University Changchun Jilin 130041 People’s Republic of China 2 Department of Oncology & Radiotherapy Qingdao Central Medical Group Qingdao Shandong 266000 People’s Republic of China 3 Department of Outpatient Qingdao Special Service Sanatorium of PLA Navy Qingdao Shandong 266071 People’s Republic of China 4 Department of Clinical Laboratory Jinan Jigang Hospital Jinan Shandong 250101 People’s Republic of China 5 Department of Oncology The Second Hospital of Dalian Medical University Dalian Liaoning 116023 People’s Republic of China

Fan H, Hou J, Liu S, Xiao Z, Cui *** Manag Res. 2020;12:8363–*** Editor and Publisher ofCancer Management and Researchwish to retract the published article. Concerns were raised regarding the integrity of the flow cytometry data shown in the article. In addition, there were also concerns regarding the duplication of images in Figure 5D with those from Figure 6D in Luo et al (2020) (https://***/10.2147/OTT.S278582). Specifically,Figure 5D, PC-3, #1, appears to have been duplicated with a similar image in Figure 6D, SW480, left hand panel, from Luo et al (2020).The authors did not respond to our queries and the decision was made to retract the article and the authors were notified of *** decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on *** retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

关键词： DARS antisense rna 1 non-coding rna cerna theory target therapy

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Expression profiling of long non-coding rna identifies linc-RoR as a prognostic biomarker in oral cancer

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TUMOR BIOLOGY 2017年第4期39卷

作者： Arunkumar, Ganesan Rao, Arunagiri Kuha Deva Magendhra Manikandan, Mayakannan Arun, Kanagaraj Vinothkumar, Vilvanathan Revathidevi, Sundaramoorthy Rajkumar, Kottayasamy Seenivasagam Rajaraman, Ramamurthy Munirajan, Arasambattu Kannan Univ Madras Dr ALM PG Inst Basic Med Sci Dept Genet Taramani Campus Madras 600113 Tamil Nadu India Royapettah Govt Hosp Ctr Oncol Madras Tamil Nadu India Kilpauk Med Coll Madras Tamil Nadu India

Oral squamous cell carcinoma is the most aggressive cancer that is associated with high recurrence, metastasis, and poor treatment outcome. Dysregulation of long non-coding rnas has been shown to promote tumor growth and metastasis in several cancers. In this study, we investigated the expression of 11 selected long non-coding rnas that are associated with cell proliferation, metastasis, and tumor suppression in oral squamous cell carcinomas and normal tissues by quantitative real-time polymerase chain reaction. Out of the 11 long non-coding rnas profiled, 9 were significantly overexpressed in tumors with tobacco chewing history. Moreover, the long non-coding rna profile was similar to the head and neck cancer datasets of The Cancer Genome Atlas database. Linc-RoR, a regulator of reprogramming, implicated in tumorigenesis was found to be overexpressed in undifferentiated tumors and showed strong association with tumor recurrence and poor therapeutic response. In oral squamous cell carcinomas, for the first time, we observed linc-RoR overexpression, downregulation of miR-145-5p, and overexpression of c-Myc, Klf4, Oct4, and Sox2, suggesting the existence of linc-RoR-mediated competing endogenous rna network in undifferentiated tumors. Taken together, this study demonstrated the association of linc-RoR overexpression in undifferentiated oral tumors and its prognostic value to predict the therapeutic response.

关键词： non-coding rna long non-coding rna oral cancer tobacco chewing stemness cancer stem cells biomarker prognosis

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non-coding transcription characterization and annotation A guide and web resource for non-coding rna databases

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rna BIOLOGY 2012年第3期9卷 274-282页

作者： Paschoal, Alexandre Rossi Maracaja-Coutinho, Vinicius Setubal, Joao Carlos Paulino Simoes, Zila Luz Verjovski-Almeida, Sergio Durham, Alan Mitchell Univ Sao Paulo Inst Matemat & Estat Dept Ciencia Comp Sao Paulo Brazil Univ Sao Paulo Inst Quim Dept Bioquim BR-01498 Sao Paulo Brazil Univ Tecnol Fed Parana Cornelio Procopio Brazil Univ Sao Paulo Fac Filosofia Ciencias & Letras Ribeirao Preto Dept Biol Sao Paulo Brazil Univ Sao Paulo Inst Matemat & Estat Programa Interunidades Bioinformat Sao Paulo Brazil

Large-scale transcriptome projects have shown that the number of rna transcripts not coding for proteins (non-coding rnas) is much larger than previously recognized. High-throughput technologies, coupled with bioinformatics approaches, have produced increasing amounts of data, highlighting the role of non-coding rnas (ncrnas) in biological processes. Data generated by these studies include diverse non-coding rna classes from organisms of different kingdoms, which were obtained using different experimental and computational assays. This has led to a rapid increase of specialized rna databases. The fast growth in the number of available databases makes integration of stored information a difficult task. We present here NRDR, a non-coding rna Databases Resource for information retrieval on ncrna databases (***). We performed a survey of 102 public databases on ncrnas and we have introduced four categorizations to classify these databases and to help researchers quickly search and find the information they need: rna family, information source, information content and available search mechanisms. NRDR is a useful databases searching tool that will facilitate research on ncrnas.

关键词： ncrna non-coding rna database transcription bioinformatics web tool

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Cancer-linked satellite 2 DNA hypomethylation does not regulate Sat2 non-coding rna expression and is initiated by heat shock pathway activation

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EPIGENETICS 2012年第8期7卷 903-913页

作者： Tilman, Gaelle Arnoult, Nausica Lenglez, Sandrine Van Beneden, Amandine Loriot, Axelle De Smet, Charles Decottignies, Anabelle Catholic Univ Louvain Fac Pharm & Biomed Sci de Duve Inst Genet & Epigenet Alterat Genomes Res Grp Brussels Belgium

Epigenetic dysfunctions, including DNA methylation alterations, play major roles in cancer initiation and progression. Although it is well established that gene promoter demethylation activates transcription, it remains unclear whether hypomethylation of repetitive heterochromatin similarly affects expression of non-coding rna from these loci. Understanding how repetitive non-coding rnas are transcriptionally regulated is important given that their established upregulation by the heat shock (HS) pathway suggests important functions in cellular response to stress, possibly by promoting heterochromatin reconstruction. We found that, although pericentromeric satellite 2 (Sat2) DNA hypomethylation is detected in a majority of cancer cell lines of various origins, DNA methylation loss does not constitutively hyperactivate Sat2 expression, and also does not facilitate Sat2 transcriptional induction upon heat shock. In melanoma tumor samples, our analysis revealed that the HS response, frequently upregulated in tumors, is probably the main determinant of Sat2 rna expression in vivo. Next, we tested whether HS pathway hyperactivation may drive Sat2 demethylation. Strikingly, we found that both hyperthermia and hyperactivated RasV12 oncogene, another potent inducer of the HS pathway, reduced Sat2 methylation levels by up to 27% in human fibroblasts recovering from stress. Demethylation occurred locally on Sat2 repeats, resulting in a demethylation signature that was also detected in cancer cell lines with moderate genome-wide hypomethylation. We therefore propose that upregulation of Sat2 transcription in response to HS pathway hyperactivation during tumorigenesis may promote localized demethylation of the locus. This, in turn, may contribute to tumorigenesis, as demethylation of Sat2 was previously reported to favor chromosomal rearrangements.

关键词： DNA hypomethylation pericentromeric satellite DNA non-coding rna heat shock response Ras oncogene

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