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Overview of noncoding RNAs involved in the osteogenic differentiation of periodontal ligament stem cells

World Journal of Stem Cells 2020年第4期12卷 251-265页

作者： Wei Qiu Bu-Ling Wu Fu-Chun Fang Department of Stomatology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support *** major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal *** periodontal ligament(PDL)tissue possesses periodontal regenerative properties,and periodontal ligament stem cells(PDLSCs)with the capacity for osteogenic differentiation show strong potential in clinical application for periodontium repair and *** RNAs(ncRNAs),which include a substantial portion of poly-A tail mature RNAs,are considered“transcriptional noise.”Recent studies show that ncRNAs play a major role in PDLSC differentiation;therefore,exploring how ncRNAs participate in the osteogenic differentiation of PDLSCs may help to elucidate the underlying mechanism of the osteogenic differentiation of PDLSCs and further shed light on the potential of stem cell transplantation for periodontium *** this review paper,we discuss the history of PDLSC research and highlight the regulatory mechanism of ncRNAs in the osteogenic differentiation of PDLSCs.

关键词： noncoding RNAs Periodontal regeneration Periodontal ligament stem cells Osteogenic differentiation

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Regulation of noncoding RNAs in innate lymphoid cells

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Cellular & Molecular Immunology 2023年第5期20卷 543-545页

作者： Benyu Liu Lingwei Zhang Pingping Zhu Zusen Fan Research Center of Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450001China school of Life Sciences Zhengzhou UniversityZhengzhou 45oo01China.Key Laboratory of Infection and Immunity of CASCAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Bejing 100049China

Innate lymphoid cells(ILCs)have been defined in recent years and are important effector cells against pathogens and critical regulators in maintaining tissue homeostasis[1].noncoding RNAs(ncRNAs),such as circular RNAs(circRNAs),long noncoding RNAs(lncRNAs),and microRNAs(miRNAs),in ILCs are emerging and have been described to function in ILC *** ncRNAs are distributed with unique patterns in ILCs and function in different molecular *** research evidence demonstrates that ncRNA dysregulation links ILC-mediated immune responses and diseases.

关键词： lymphoid homeostasis noncoding

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Different types of disease-causing noncoding variants revealed by genomic and gene expression analyses in families with X-linked intellectual disability

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HUMAN MUTATION 2021年第7期42卷 835-847页

作者： Field, Michael J. Kumar, Raman Hackett, Anna Kayumi, Sayaka Shoubridge, Cheryl A. Ewans, Lisa J. Ivancevic, Atma M. Dudding-Byth, Tracy Carroll, Renee Kroes, Thessa Gardner, Alison E. Sullivan, Patricia Ha, Thuong T. Schwartz, Charles E. Cowley, Mark J. Dinger, Marcel E. Palmer, Elizabeth E. Christie, Louise Shaw, Marie Roscioli, Tony Gecz, Jozef Corbett, Mark A. NSW Genet Learning Disabil Serv Newcastle NSW Australia Univ Adelaide Adelaide Med Sch Adelaide SA Australia Univ Adelaide Robinson Res Inst Adelaide SA Australia Univ Newcastle Sch Biomed Sci & Pharm Newcastle NSW Australia Univ New South Wales St Vincents Clin Sch Darlinghurst NSW Australia Garvan Inst Med Res Kinghorn Ctr Clin Genom Darlinghurst NSW Australia Univ Colorado Dept Mol Cellular & Dev Biol Boulder CO USA Univ New South Wales Childrens Canc Inst Kensington NSW Australia SA Pathol Ctr Canc Biol Mol Pathol Dept Adelaide SA Australia Greenwood Genet Ctr Greenwood SC USA Univ New South Wales Sch Biotechnol & Biomol Sci Kensington NSW Australia Univ New South Wales Sch Womens & Childrens Hlth Sydney NSW Australia Univ New South Wales NeuRA Sydney NSW Australia Sydney Childrens Hosp Ctr Clin Genet Sydney NSW Australia South Australian Hlth & Med Res Inst Adelaide SA Australia

The pioneering discovery research of X-linked intellectual disability (XLID) genes has benefitted thousands of individuals worldwide;however, approximately 30% of XLID families still remain unresolved. We postulated that noncoding variants that affect gene regulation or splicing may account for the lack of a genetic diagnosis in some cases. Detecting pathogenic, gene-regulatory variants with the same sensitivity and specificity as structural and coding variants is a major challenge for Mendelian disorders. Here, we describe three pedigrees with suggestive XLID where distinctive phenotypes associated with known genes guided the identification of three different noncoding variants. We used comprehensive structural, single-nucleotide, and repeat expansion analyses of genome sequencing. RNA-Seq from patient-derived cell lines, reverse-transcription polymerase chain reactions, Western blots, and reporter gene assays were used to confirm the functional effect of three fundamentally different classes of pathogenic noncoding variants: a retrotransposon insertion, a novel intronic splice donor, and a canonical splice variant of an untranslated exon. In one family, we excluded a rare coding variant in ARX, a known XLID gene, in favor of a regulatory noncoding variant in OFD1 that correlated with the clinical phenotype. Our results underscore the value of genomic research on unresolved XLID families to aid novel, pathogenic noncoding variant discovery.

关键词： gene regulation intellectual disability noncoding RNA‐ Seq splicing transcriptome whole‐ genome sequencing X‐ linked

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Prediction of small, noncoding RNAs in bacteria using heterogeneous data

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JOURNAL OF MATHEMATICAL BIOLOGY 2008年第1-2期56卷 183-200页

作者： Tjaden, Brian Wellesley Coll Dept Comp Sci Wellesley MA 02481 USA

sRNAFinder is a new gene prediction system for systematic identification of noncoding genes in bacteria. Most noncoding RNAs in prokaryotes belong to a class of genes denoted as small RNAs (sRNAs). In the model organism Escherichia coli, over 70 sRNA genes have been identified, and the existence of many more has been hypothesized. While various sources of information have proven useful for prediction of novel sRNA genes, most computational approaches do not take advantage of the disparate sources of data available for identifying these noncoding RNA genes. We present a general probabilistic method for predicting sRNA genes in bacteria. The method, based on a general Markov model, is implemented in the computational tool sRNAFinder. sRNAFinder incorporates heterogeneous data sources for gene prediction, including primary sequence data, transcript expression data from microarray experiments, and conserved RNA structure information as determined from comparative genomics analysis. We demonstrate that sRNAFinder improves upon current tools for identifying small, noncoding genes in bacteria.

关键词： sRNA noncoding RNA gene genefinder Markov model Hfq

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Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder

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NEUROGENETICS 2018年第1期19卷 17-26页

作者： Griswold, Anthony J. Van Booven, Derek Cuccaro, Michael L. Haines, Jonathan L. Gilbert, John R. Pericak-Vance, Margaret A. Univ Miami Miller Sch Med John P Hussman Inst Human Genom Miami FL 33136 USA Univ Miami Miller Sch Med Dept Human Genet Dr John T Macdonald Fdn Miami FL 33136 USA Case Western Reserve Univ Dept Epidemiol & Biostat Cleveland OH 44106 USA

Alterations of the gamma-aminobutyric acid (GABA) signaling system has been strongly linked to the pathophysiology of autism spectrum disorder (ASD). Genetic associations of common variants in GABA receptor subunits, in particular GABRA4 on chromosome 4p12, with ASD have been replicated by several studies. Moreover, molecular investigations have identified altered transcriptional and translational levels of this gene and protein in brains of ASD individuals. Since the genotyped common variants are likely not the functional variants contributing to the molecular consequences or underlying ASD phenotype, this study aims to examine rare sequence variants in GABRA4, including those outside the protein coding regions of the gene. We comprehensively re-sequenced the entire protein coding and noncoding portions of the gene and putative regulatory sequences in 82 ASD individuals and 55 developmentally typical pediatric controls, all homozygous for the most significant previously associated ASD risk allele (G/G at rs1912960). We identified only a single common, coding variant, and no association of any single marker or set of variants with ASD. Functional annotation of noncoding variants identified several rare variants in putative regulatory sites. Finally, a rare variant unique to ASD cases, in an evolutionary conserved site of the 3'UTR, shows a trend toward decreasing gene expression. Hence, GABRA4 rare variants in noncoding DNA may be variants of modest physiological effects in ASD etiology.

关键词： Autism GABRA4 Sequencing noncoding

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The Role of De Novo noncoding Regulatory Mutations in Neurodevelopmental Disorders

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TRENDS IN NEUROSCIENCES 2019年第2期42卷 115-127页

作者： Turner, Tychele N. Eichler, Evan E. Univ Washington Sch Med Dept Genome Sci Seattle WA USA Univ Washington Howard Hughes Med Inst Seattle WA 98195 USA

Advances in sequencing technology have significantly expanded our understanding of the genetics of autism and neurodevelopmental disorders (NDDs). Continued technological improvements and cost reductions have now shifted the focus to investigations into the functional noncoding portions of the genome. There is a patient trend toward an excess of de novo and potentially disruptive mutations among conserved noncoding sequences implicated in the regulation of genes. The signals become stronger when restricted to genes already implicated in NDDs, but de novo mutation in such elements is estimated to account for < 5% of patients. Larger sample sizes, improved variant detection, functional testing, and better approaches to classify noncoding variation will be required to identify specific pathogenic variants underlying disease.

关键词： autism neurodevelopmental disorders noncoding regulatory mutations genome sequencing genetic architecture

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Divergent contributions of coding and noncoding sequences to initial high-altitude adaptation in passerine birds endemic to the Qinghai-Tibet Plateau

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MOLECULAR ECOLOGY 2023年第13期32卷 3524-3540页

作者： Hao, Yan Song, Gang Zhang, Yong E. Zhai, Weiwei Jia, Chenxi Ji, Yanzhu Tang, Shiyu Lv, Hongrui Qu, Yanhua Lei, Fumin Chinese Acad Sci Inst Zool Key Lab Zool Systemat & Evolut Beijing Peoples R China Univ Chinese Acad Sci Coll Life Sci Beijing Peoples R China Chinese Acad Sci Ctr Excellence Anim Evolut & Genet Kunming Peoples R China

Early events in the evolution of an ancestral lineage can shape the adaptive patterns of descendant species, but the evolutionary mechanisms driving initial adaptation from an ancestor remain largely unexplored. High-altitude adaptations have been extensively explored from the viewpoint of protein-coding genes;however, the contribution of noncoding regions remains relatively neglected. Here, we integrate genomic and transcriptomic data to investigate adaptive evolution in the ancestor of three high-altitude snowfinch species endemic to the Qinghai-Tibet Plateau. Our genome-wide scan for adaptation in the snowfinch ancestor identifies strong adaptation signals in functions of development and metabolism for the coding genes, but in functions of the nervous system development for noncoding regions. This pattern is exclusive to the snowfinch ancestor compared to a control ancestral lineage subject to weak selection. Changes in noncoding regions in the snowfinch ancestor, especially those nearest to coding genes, may be disproportionately associated with the differential expression of genes in the brain tissue compared to other tissues. Extensive gene expression in the brain tissue can be further altered via genetic regulatory networks of transcription factors harbouring potential accelerated regulatory regions (e.g., the development-related transcription factor YEATS4). Altogether, our study provides new evidence concerning how coding and noncoding sequences work through decoupled pathways in initial adaptation to the selective pressure of high-altitude environments. The analysis highlights the idea that noncoding sequences may be promising elements in facilitating the rapid evolution and adaptation to high altitudes.

关键词： adaptive evolution brain gene expression high altitude noncoding

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TFIIF Facilitates Dissociation of RNA Polymerase II from noncoding RNAs That Lack a Repression Domain

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MOLECULAR AND CELLULAR BIOLOGY 2010年第1期30卷 91-97页

作者： Wagner, Stacey D. Kugel, Jennifer F. Goodrich, James A. Univ Colorado Dept Chem & Biochem Boulder CO 80309 USA

noncoding RNAs (ncRNAs) have recently been found to regulate multiple steps in mammalian mRNA transcription. Mouse B2 RNA and human Alu RNA bind RNA polymerase II (Pol II) and repress mRNA transcription, using regions of the ncRNAs referred to as repression domains. Two other ncRNAs, mouse B1 RNA and human small cytoplasmic Alu (scAlu) RNA, bind Pol II with high affinity but lack repression domains and hence do not inhibit transcription. To better understand the interplay between ncRNAs that bind Pol II and their functions in transcription, we studied how Pol II binding and transcriptional repression are controlled by general transcription factors. We found that TFIIF associates with B1 RNA/Pol II and scAlu RNA/Pol II complexes and decreases their kinetic stability. Both subunits of TFIIF are required for this activity. Importantly, fusing a repression domain to B1 RNA stabilizes its interaction with Pol II in the presence of TFIIF. These results suggest a new role for TFIIF in regulating the interaction of ncRNAs with Pol II;specifically, it destabilizes interactions with ncRNAs that are not transcriptional repressors. These studies also identify a new function for ncRNA repression domains: they stabilize interactions of ncRNAs with Pol II in the presence of TFIIF.

关键词： .Facilitates noncoding repression domains scAlu bind Pol II RNA/Pol

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Evolution of noncoding and silent coding sites in the Plasmodium falciparum and Plasmodium reichenowi genomes

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MOLECULAR BIOLOGY AND EVOLUTION 2005年第7期22卷 1621-1626页

作者： Neafsey, DE Hartl, DL Berriman, M Harvard Univ Dept Organism & Evolutionary Biol Cambridge MA 02138 USA Wellcome Trust Sanger Inst Hinxton England

We compared levels of sequence divergence between fourfold synonymous coding sites and noncoding sites from the intergenic and intronic regions of the Plasmodium falcipartim and Plasmodium reichenowi genomes. We observed significant differences in the level of divergence between these classes of silent sites. Fourfold synonymous coding sites exhibited the highest level of sequence divergence, followed by introns, and then intergenic sequences. This pattern of relative divergence rates has been observed in primate genomes but was unexpected in Plasmodium due to a paucity of variation at silent sites in P. falciparum and the corollary hypothesis that silent sites in this genome may be subject to atypical selective constraints. Exclusion of hypermutable CpG dinucleotides reduces the divergence level of synonymous coding sites to that of intergenic sites but does not diminish the significantly higher divergence level of introns relative to intergenic sites. A greater than expected incidence of CpG dinucleotides in intergenic regions less than 500 bp from genes may indicate selective maintenance of regulatory motifs containing CpGs. Divergence rates of different classes of silent sites in these Plasmodium genomes are determined by a combination of mutational and selective pressures.

关键词： malaria plasmodium reichenowi noncoding divergence introns

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The Large Mitochondrial Genome of Symbiodinium minutum Reveals Conserved noncoding Sequences between Dinoflagellates and Apicomplexans

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GENOME BIOLOGY AND EVOLUTION 2015年第8期7卷 2237-2244页

作者： Shoguchi, Eiichi Shinzato, Chuya Hisata, Kanako Satoh, Nori Mungpakdee, Sutada Okinawa Inst Sci & Technol Grad Univ Marine Genom Unit Onna Okinawa Japan

Even though mitochondrial genomes, which characterize eukaryotic cells, were first discovered more than 50 years ago, mitochondrial genomics remains an important topic in molecular biology and genome sciences. The Phylum Alveolata comprises three major groups (ciliates, apicomplexans, and dinoflagellates), the mitochondrial genomes of which have diverged widely. Even though the gene content of dinoflagellate mitochondrial genomes is reportedly comparable to that of apicomplexans, the highly fragmented and rearranged genome structures of dinoflagellates have frustrated whole genomic analysis. Consequently, noncoding sequences and gene arrangements of dinoflagellate mitochondrial genomes have not been well characterized. Here we report that the continuous assembled genome (similar to 326 kb) of the dinoflagellate, Symbiodinium minutum, is AT-rich (similar to 64.3%) and that it contains three protein-coding genes. Based upon in silico analysis, the remaining 99% of the genome comprises transcriptomic noncoding sequences. RNA edited sites and unique, possible start and stop codons clarify conserved regions among dinoflagellates. Our massive transcriptome analysis shows that almost all regions of the genome are transcribed, including 27 possible fragmented ribosomal RNA genes and 12 uncharacterized small RNAs that are similar to mitochondrial RNA genes of the malarial parasite, Plasmodium falciparum. Gene map comparisons show that gene order is only slightly conserved between S. minutum and P. falciparum. However, small RNAs and intergenic sequences share sequence similarities with P. falciparum, suggesting that the function of noncoding sequences has been preserved despite development of very different genome structures.

关键词： Symbiodinium Plasmodium mitochondrial genome expansion RNA editing gene map noncoding

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