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Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan
Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches...
2018: Frontiers in Immunology
Alvaro Orell, Vanessa Tripp, Victor Aliaga-Tobar, Sonja-Verena Albers, Vinicius Maracaja-Coutinho, Lennart Randau
Non-coding RNAs (ncRNA) are involved in essential biological processes in all three domains of life. The regulatory potential of ncRNAs in Archaea is, however, not fully explored. In this study, RNA-seq analyses identified a set of 29 ncRNA transcripts in the hyperthermophilic archaeon Sulfolobus acidocaldarius that were differentially expressed in response to biofilm formation. The most abundant ncRNA of this set was found to be resistant to RNase R treatment (RNase R resistant RNA, RrrR(+)) due to duplex formation with a reverse complementary RNA (RrrR(-))...
February 26, 2018: Nucleic Acids Research
Steven Parker, Marcin G Fraczek, Jian Wu, Sara Shamsah, Alkisti Manousaki, Kobchai Dungrattanalert, Rogerio Alves de Almeida, Edith Invernizzi, Tim Burgis, Walid Omara, Sam Griffiths-Jones, Daniela Delneri, Raymond T O'Keefe
Noncoding RNAs (ncRNAs) are emerging as key regulators of cellular function. We have exploited the recently developed barcoded ncRNA gene deletion strain collections in the yeast Saccharomyces cerevisiae to investigate the numerous ncRNAs in yeast with no known function. The ncRNA deletion collection contains deletions of tRNAs, snoRNAs, snRNAs, stable unannotated transcripts (SUTs), cryptic unannotated transcripts (CUTs) and other annotated ncRNAs encompassing 532 different individual ncRNA deletions. We have profiled the fitness of the diploid heterozygous ncRNA deletion strain collection in six conditions using batch and continuous liquid culture, as well as the haploid ncRNA deletion strain collections arrayed individually onto solid rich media...
March 12, 2018: PLoS Genetics
Priyanka Kumari, Subodh Kumar Singh, Rajiva Raman
BACKGROUND: Genome-wide linkage analysis and whole genome sequencing in a Van der Woude syndrome (VWS) family revealed that the SNP, rs539075, within intron 2 of the cadherin 2 gene (CDH2) co-segregated with the disease phenotype. RESULTS: A study with nonsyndromic cleft lip with or without cleft palate (NSCL ± P) cases (N = 292) and controls (N = 287) established association of this SNP with NSCL ± P as a risk factor. RT-PCR based expression analysis of the SNP-harbouring region of intron 2 of CDH2 in the clefted lip and/or palate tissues of 16 patients revealed that the mutant allele expressed in all those individuals having it (hetero-/homozygous), whereas the wild type allele expressed in <50% of the samples in which it was present...
March 7, 2018: Gene
Wei Liu, Li Li, Xuhe Long, Weixin You, Yuexian Zhong, Menglin Wang, Huan Tao, Shoukai Lin, Huaqin He
Network-based systems biology has become an important method for analyzing high-throughput gene expression data and gene function mining. Escherichia coli ( E. coli ) has long been a popular model organism for basic biological research. In this paper, weighted gene co-expression network analysis (WGCNA) algorithm was applied to construct gene co-expression networks in E. coli . Thirty-one gene co-expression modules were detected from 1391 microarrays of E. coli data. Further characterization of these modules with the database for annotation, visualization, and integrated discovery (DAVID) tool showed that these modules are associated with several kinds of biological processes, such as carbohydrate catabolism, fatty acid metabolism, amino acid metabolism, transportation, translation, and ncRNA metabolism...
March 8, 2018: Cells
Petros Takousis
Changes associated with neurodegeneration at the cellular level are manifestations of deregulated biochemical pathways, and typically precede neuronal loss. Incorporation of molecular markers in the diagnostic process could aid detection of early changes, prior to extensive neuronal loss, as early as the presymptomatic stages of the disorder, thus enabling improved patient stratification for targeted drug development. Such biomarkers should be sufficiently sensitive and specific to distinguish AD from other disorders with overlapping symptoms...
2018: Methods in Molecular Biology
Taichi Hagio, Shun Sakuraba, Junichi Iwakiri, Ryota Mori, Kiyoshi Asai
BACKGROUND: It is known that functional RNAs often switch their functions by forming different secondary structures. Popular tools for RNA secondary structures prediction, however, predict the single 'best' structures, and do not produce alternative structures. There are bioinformatics tools to predict suboptimal structures, but it is difficult to detect which alternative secondary structures are essential. RESULTS: We proposed a new computational method to detect essential alternative secondary structures from RNA sequences by decomposing the base-pairing probability matrix...
February 19, 2018: BMC Bioinformatics
Ding-Qi Wang, Peng Fu, Chengye Yao, Ling-Shuang Zhu, Tong-Yao Hou, Jian-Guo Chen, Youming Lu, Dan Liu, Ling-Qiang Zhu
Long non-coding RNA (lncRNA) is a kind of non-coding RNA (ncRNA), with a length of 200 nt to 100 kb, that lacks a significant open reading frame (ORF) encoding a protein. lncRNAs are widely implicated in various physiological and pathological processes, such as epigenetic regulation, cell cycle regulation, cell differentiation regulation, cancer, and neurodegenerative diseases, through their interactions with chromatin, protein, and other RNAs. Numerous studies have suggested that lncRNAs are closely linked with the occurrence and development of a variety of diseases, especially neurodegenerative diseases, of which the etiologies are complicated and the underlying mechanisms remain elusive...
March 2, 2018: Molecular Therapy. Nucleic Acids
Alexandra Iulia Irimie, Alina-Andreea Zimta, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Cornelia Braicu, Ioana Berindan-Neagoe
Previously ignored non-coding RNAs (ncRNAs) have become the subject of many studies. However, there is an imbalance in the amount of consideration that ncRNAs are receiving. Some transcripts such as microRNAs (miRNAs) or small interfering RNAs (siRNAs) have gained much attention, but it is necessary to investigate other "pieces of the RNA puzzle". These can offer a more complete view over normal and pathological cell behavior. The other ncRNA species are less studied, either due to their recent discovery, such as stable intronic sequence RNA (sisRNA), YRNA, miRNA-offset RNAs (moRNA), telomerase RNA component (TERC), natural antisense transcript (NAT), transcribed ultraconserved regions (T-UCR), and pseudogene transcript, or because they are still largely seen as non-coding transcripts with no relevance to pathogenesis...
March 1, 2018: Genes
Erich Michel, Olivier Duss, Frédéric H-T Allain
Posttranscriptional regulation of gene expression by small noncoding RNAs (sRNAs) is an important control mechanism that modulates bacterial metabolism, motility, and pathogenesis. Using the bacterial carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) system, we here describe an E. coli-based cell-free translation assay that allows a quantitative analysis of translation regulation by ncRNAs and their corresponding translation repressor proteins. The assay quantifies the translation of chloramphenicol acetyltransferase in cell-free expression reactions that contain defined amounts of ncRNA and repressor protein...
2018: Methods in Molecular Biology
Michael K Skinner, Millissia Ben Maamar, Ingrid Sadler-Riggleman, Daniel Beck, Eric Nilsson, Margaux McBirney, Rachel Klukovich, Yeming Xie, Chong Tang, Wei Yan
BACKGROUND: Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm. METHODS: Gestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated...
February 27, 2018: Epigenetics & Chromatin
Padmanaban S Suresh, Rie Tsutsumi, Thejaswini Venkatesh
YBX1 (Y box binding protein 1) is an RNA-/DNA-binding multifunctional protein harboring the classical cold shock protein (CSD) domain, an A/P domain, and a long C-terminal domain with alternating positively and negatively charged amino acids. It is a well-established oncogenic transcriptional factor, and regulates apoptosis, translation, cell proliferation, mRNA splicing, repair, differentiation, and stress response. The non-coding transcriptome has added yet another layer of complexity to the YBX1-mediated master regulation of cellular functions...
February 19, 2018: European Journal of Cell Biology
Mahshid Malakootian, Fatemeh Mirzadeh Azad, Youssef Fouani, Elham Taheri Bajgan, Hooshang Saberi, Seyed Javad Mowla
Long non-coding RNAs (lncRNAs) are important modulators of various cellular and molecular events, including cancer-associated pathways. The Anti-differentiation ncRNA (ANCR) is a key regulator of keratinocyte differentiation, where its expression is necessary to maintain epidermal progenitor's cells. Herein, we investigated the expression pattern of ANCR in the course of neural differentiation. Moreover, we used published RNAseq data and clinical samples to evaluate the alteration of ANCR expression in different cell types and brain tumors...
February 23, 2018: Journal of Neuro-oncology
Yang Zhao, William Dunker, Yi-Tao Yu, John Karijolich
Pseudouridine is the most abundant internal RNA modification in stable noncoding RNAs (ncRNAs). It can be catalyzed by both RNA-dependent and RNA-independent mechanisms. Pseudouridylation impacts both the biochemical and biophysical properties of RNAs and thus influences RNA-mediated cellular processes. The investigation of nuclear-ncRNA pseudouridylation has demonstrated that it is critical for the proper control of multiple stages of gene expression regulation. Here, we review how nuclear-ncRNA pseudouridylation contributes to transcriptional regulation and pre-mRNA splicing...
2018: Frontiers in Bioengineering and Biotechnology
Elena Magnani, Filippo Macchi, Monica Mancini, Vanessa Lomazzi, Sara Cogliati, Christian Pistore, Martina Mandruzzato, Anne-Catherine Dock-Bregeon, Ian Marc Bonapace
Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression...
February 18, 2018: Biochimica et Biophysica Acta
Harshavardhan Janga, Marina Aznaourova, Fabian Boldt, Katrin Damm, Arnold Grünweller, Leon N Schulte
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes...
2018: PloS One
Xu Zhang, Xiancai Ma, Shuliang Jing, Hui Zhang, Yijun Zhang
Retroviruses can cause severe diseases such as cancer and acquired immunodeficiency syndrome. A unique feature in the life cycle of retroviruses is that their RNA genome is reverse transcribed into double-stranded DNA, which then integrates into the host genome to exploit the host machinery for their benefits. The metazoan genome encodes numerous non-coding RNAs (ncRNA), which act as key regulators in essential cellular processes such as antiviral response. The development of next-generation sequencing technology has greatly accelerated the detection of ncRNAs from viruses and their hosts...
February 9, 2018: Retrovirology
Noreen F Rizvi, John A Howe, Ali Nahvi, Daniel J Klein, Thierry O Fischmann, Hai-Young Kim, Mark A McCoy, Scott S Walker, Alan Hruza, Matthew P Richards, Chad Chamberlin, Peter Saradjian, Margaret T Butko, Gabriel Mercado, Julja Burchard, Corey Strickland, Peter J Dandliker, Graham F Smith, Elliott B Nickbarg
Recent advances in understanding the relevance of non-coding RNA (ncRNA) to disease have increased interest in drugging ncRNA with small molecules. The recent discovery of ribocil, a structurally distinct synthetic mimic of the natural ligand of the flavin mononucleotide (FMN) riboswitch, has revealed the potential chemical diversity of small molecules that target ncRNA. Affinity-selection mass spectrometry (AS-MS) is theoretically applicable to high-throughput screening (HTS) of small molecules binding to ncRNA...
February 7, 2018: ACS Chemical Biology
Sylvain Fauquenoy, Valerie Migeot, Olivier Finet, Carlo Yague-Sanz, Olga Khorosjutina, Karl Ekwall, Damien Hermand
The cell fate decision leading to gametogenesis requires the convergence of multiple signals on the promoter of a master regulator. In fission yeast, starvation-induced signaling leads to the transcriptional induction of the ste11 gene, which encodes the central inducer of mating and gametogenesis, known as sporulation. We find that the long intergenic non-coding (linc) RNA rse1 is transcribed divergently upstream of the ste11 gene. During vegetative growth, rse1 directly recruits a Mug187-Lid2-Set1 complex that mediates cis repression at the ste11 promoter through SET3C-dependent histone deacetylation...
January 18, 2018: Current Biology: CB
Juan José González Plaza
Intercellular communication is a widespread phenomenon in all domains of Life. Bacteria have developed many ways of communicating with one another and with other species, either prokaryotic or eukaryotic. RNA has been a key molecule since beginning of Life on Earth, and is one of the carriers of information. Given the current antibiotic crisis, understanding the way in which pathogens communicate can lead towards improved ways to control infections when antimicrobial therapy is not possible. Different subspecies of RNA, non-coding, and of small size, designated here as ncRNAs, have been in the recent years subject of a great research effort, and results have contributed to a growing field of knowledge...
January 30, 2018: FEMS Microbiology Letters
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