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X Chromosome Dosage Compensation: How Mammals Keep the Balance

ANNUAL REVIEW OF GENETICS 2008年第1期42卷 733-772页

作者： Payer, Bernhard Lee, Jeannie T. Massachusetts Gen Hosp Dept Mol Biol Howard Hughes Med Inst Boston MA 02114 USA Harvard Univ Sch Med Dept Genet Boston MA 02114 USA

The development of genetic sex determination and cytologically distinct sex chromosomes leads to the potential problem of gene dosage imbalances between autosomes and sex chromosomes and also between males and females. To circumvent these imbalances, mammals have developed an elaborate system of dosage compensation that includes both upregulation and repression of the X chromosome. Recent advances have provided insights into the evolutionary history of how both the imprinted and random forms of X chromosome inactivation have come about. Furthermore, our understanding of the epigenetic switch at the X-inactivation center and the molecular aspects of chromosome-wide silencing has greatly improved recently. Here, we review various facets of the ever-expanding field of mammalian dosage compensation and discuss its evolutionary, developmental, and mechanistic components.

关键词： X chromosome inactivation epigenetics imprinting evolution chromatin noncoding rna

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Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class

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MOLECULAR CELL 2017年第2期65卷 220-230页

作者： Nelson, James W. Atilho, Ruben M. Sherlock, Madeline E. Stockbridge, Randy B. Breaker, Ronald R. Yale Univ Dept Mol Cellular & Dev Biol New Haven CT 06520 USA Yale Univ Dept Mol Biophys & Biochem New Haven CT 06520 USA Univ Michigan Dept Biophys Ann Arbor MI 48109 USA Univ Michigan Dept Mol Cellular & Dev Biol Ann Arbor MI 48109 USA Yale Univ Howard Hughes Med Inst New Haven CT 06520 USA

The guanidyl moiety is a component of fundamental metabolites, including the amino acid arginine, the energy carrier creatine, and the nucleobase guanine. Curiously, reports regarding the importance of free guanidine in biology are sparse, and no biological receptors that specifically recognize this compound have been previously identified. We report that many members of the ykkC motif rna, the longest unresolved riboswitch candidate, naturally sense and respond to guanidine. This rna is found throughout much of the bacterial domain of life, where it commonly controls the expression of proteins annotated as urea carboxylases and multidrug efflux pumps. Our analyses reveal that these proteins likely function as guanidine carboxylases and guanidine transporters, respectively. Furthermore, we demonstrate that bacteria are capable of endogenously producing guanidine. These and related findings demonstrate that free guanidine is a biologically relevant compound, and several gene families that can alleviate guanidine toxicity exist.

关键词： aptamer EmrE multidrug efflux noncoding rna orphan riboswitch SugE urea carboxylase ykkC

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Novel circular rna expression profile of uveal melanoma revealed by microarray

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Chinese Journal of Cancer Research 2018年第6期30卷 656-668页

作者： Xuan Yang Yang Li Yueming Liu Xiaolin Xu Yingzhi Wang Yanni Yan Wenjia Zhou Jingyan Yang Wenbin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology & Visual Sciences Key LabBeijing Tongren HospitalCapital Medical University Beijing Institute of Ophthalmology Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology & Visual Sciences Key Laboratory

Objective: The present study aimed to investigate circular rna(circrna) expression in uveal melanoma(UM).Methods: First,we used microarray to compare the expression profiles of circrna in five UM samples and five normal uvea ***,bioinformatics analyses,including gene ontology(GO) analysis and pathway analysis,were applied to study these differentially expressed circrnas to predict pathogenic pathways that may be *** real-time polymerase chain reaction(qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circrna expression profiles obtained from the microarray ***,we analyzed the interaction between validated circrnas and their potential cancer-associated mirna ***: In total,50,579 circrnas [fold change(FC) ≥2.0; P<0.05],including 20,654 up-regulated and 29,925 down-regulated circrnas,were identified as differentially expressed between UM tissues and normal uvea *** used qRT-PCR to verify seven dysregulated circrnas indicated by the microarray data,including hsacirc0119873,hsacirc0128533,hsacirc0047924,hsacirc0103232,hsa-circrna10628-6,hsacirc0032148 and hsacirc0133460,which may be promising candidates to study future molecular ***: This study explored,for the first time,the abnormal expression of circrnas in UM and described the expression profile of circrnas,providing a new potential target for the mechanism of UM and future treatment of UM.

关键词： Uveal melanoma circular rna microarray noncoding rna

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Regulation of Transcription by rna Polymerase III Promotors in the Norm and Pathology

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MOLECULAR BIOLOGY 2024年第2期58卷 192-204页

作者： Schwartz, A. M. Tatosyan, K. A. Stasenko, D. V. Kramerov, D. A. Russian Acad Sci Engelhardt Inst Mol Biol Moscow 119991 Russia Univ Haifa Fac Nat Sci Dept Human Biol IL-3498838 Haifa Israel Technion Israel Inst Technol Rappaport Fac Med Dept Biochem IL-31096 Haifa Israel

rna polymerase III synthesizes a wide range of noncoding rnas shorter than 400 nucleotides in length. These rnas are involved in protein synthesis (trna, 5S rrna, and 7SL rna), maturation, and splicing of different types of rna (RPR, MRP rna, and U6 snrna), regulation of transcription (7SK rna), replication (Y rna), and intracellular transport (vault rna). BC200 and BC1 rna genes are transcribed by rna polymerase III in neurons only where these rnas regulate protein synthesis. Mutations in the regulatory elements of the genes transcribed by rna polymerase III as well as in transcription factors of this rna polymerase are associated with the development of a number of diseases, primarily oncological and neurological. In this regard, the mechanisms of regulation of the expression of the genes containing various rna polymerase III promoters were actively studied. This review describes the structural and functional classification of polymerase III promoters, as well as the factors involved in the regulation of promoters of different types. A number of examples demonstrate the role of the described factors in the pathogenesis of human diseases.

关键词： rna polymerase III genes promotors transcription factors noncoding rna mammals human pathologies

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Molecular profiling of multiple myeloma: from gene expression analysis to next-generation sequencing

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EXPERT OPINION ON BIOLOGICAL THERAPY 2013年第Sup1期13卷 S55-S68页

作者： Agnelli, Luca Tassone, Pierfrancesco Neri, Antonino Univ Milan Dept Clin Sci & Community Hlth I-20122 Milan Italy IRCCS Policlin Fdn Milan Italy Magna Graecia Univ Catanzaro Catanzaro Italy T Campanella Canc Ctr Dept Expt & Clin Med Med Oncol Unit Catanzaro Italy

Introduction: Multiple myeloma is a fatal malignant proliferation of clonal bone marrow Ig-secreting plasma cells, characterized by wide clinical, biological, and molecular heterogeneity. Areas covered: Herein, global gene and microrna expression, genome-wide DNA profilings, and next-generation sequencing technology used to investigate the genomic alterations underlying the bio-clinical heterogeneity in multiple myeloma are discussed. Expert opinion: High-throughput technologies have undoubtedly allowed a better comprehension of the molecular basis of the disease, a fine stratification, and early identification of high-risk patients, and have provided insights toward targeted therapy studies. However, such technologies are at risk of being affected by laboratory-or cohort-specific biases, and are moreover influenced by high number of expected false positives. This aspect has a major weight in myeloma, which is characterized by large molecular heterogeneity. Therefore, meta-analysis as well as multiple approaches are desirable if not mandatory to validate the results obtained, in line with commonly accepted recommendation for tumor diagnostic/prognostic biomarker studies.

关键词： gene expression profiling microrna multiple myeloma next-generation sequencing noncoding rna SNP-array genotyping

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Plasma Microrna-186 and Proteinuria in Focal Segmental Glomerulosclerosis

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AMERICAN JOUrnaL OF KIDNEY DISEASES 2015年第2期65卷 223-232页

作者： Zhang, Changming Zhang, Wanfen Chen, Hui-Mei Liu, Chunbei Wu, Junnan Shi, Shaolin Liu, Zhi-Hong Nanjing Univ Sch Med Natl Clin Res Ctr Kidney Dis Jinling Hosp Nanjing 210002 Jiangsu Peoples R China

Background: Micrornas (mirnas) are stable in circulation, and their unique expression profiles can serve as fingerprints for various diseases. This study explored whether plasma mirnas could be used as biomarkers to evaluate disease activity in patients with focal segmental glomerulosclerosis (FSGS). Study Design: Retrospective and prospective cohorts. Setting & Participants: 78 patients with FSGS with nephrotic proteinuria (protein excretion > 3.5 g/24 h), 35 patients with FSGS in complete remission, 63 patients with membranous nephropathy, 59 patients with diabetic nephropathy, and 69 apparently healthy controls were recruited. Plasma samples from 51 other patients with FSGS with nephrotic proteinuria were collected prospectively before and after steroid treatment. Predictors: Plasma mirna concentration. Outcomes: Complete remission (protein excretion < 0.4 g/24 h), or no response (sustained protein excretion. > 3.5 g/24 h after 8 weeks of steroid treatment). Measurements: Quantitative reverse transcription-polymerase chain reaction analysis of plasma mirnas. Results: Increases in miR-125b, miR-186, and miR-193a-3p levels were identified in a pooled plasma sample of 9 patients with FSGS compared with that of 9 healthy controls and were confirmed with individual samples from patients with FSGS (n = 32) and healthy controls (n = 30). Areas under the receiver operating characteristic curves of miR-125b, miR-186, miR-193a-3p, and the 3 mirnas in combination were 0.882, 0.789, 0.910, and 0.963, respectively. miR-125b and miR-186 concentrations were significantly lower in patients with FSGS in complete remission (n = 35) than those with nephrotic proteinuria (n = 37). In a prospective study, miR-125b and miR-186 levels declined markedly in patients with FSGS with complete remission (n = 29), but not those with no response (n = 22), after steroid treatment. Plasma miR-125b and miR-186 levels were not elevated in patients with membranous nephropathy (n = 63) and diabetic

关键词： Plasma miR-186 focal segmental glomerulosclerosis (FSGS) biomarkers microrna (mirna) expression profile nephrotic syndrome proteinuria remission noncoding rna circulating mirnas kidney disease

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The Use of Small noncoding rnas to Silence Transcription in Human Cells

The Use of Small Noncoding RNAs to Silence Transcription in ...

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作者： Kevin V. Morris

In human cells, small noncoding rnas have been shown to possess an ability to exert regulatory control of gene expression when they are generated to target a gene promoter specifically. Mechanistically, small rna-directed transcriptional gene suppression functions by targeting of epigenetic modifications, such as histone and DNA methylation, to a targeted promoter locus, the result of which is the restriction of the action of rna polymerase II and gene transcription specifically at the targeted gene promoter (56, 57). In human cells, this activity requires a transcriptional silencing complex that consists of Argonaute 1 (Ago-1) (54, 55), DNA methyltransferase 3A (47, 48, 56), and histone deacetylase 1 (48, 49) as well as a low-copy promoter-associated rna that is expressed and spans the rna-targeted loci (57). Importantly, as this mode of rna-directed gene regulation functions through targeted silent state epigenetic changes, it has the potential to be a longer lasting if not permanent mode of gene silencing that may also be refractory to compensatory mutations as the targeting is at the level of chromatin and not at the genes mrna level. less

关键词： Homo sapiens Transcription sirna Small rna noncoding rna DNMT3a Ago-1 HDAC-1

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Prediction of Structural noncoding rnas With rnaz

Prediction of Structural Noncoding RNAs With RNAz

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作者： Stefan Washietl

The function of many noncoding rnas (ncrnas) depend on a defined secondary structure. rnaz detects evolutionarily conserved and thermodynamically stable rna secondary structures in multiple sequence alignments and, thus, efficiently filters for candidate ncrnas. In this chapter, we provide a step-by-step guide on how to use rnaz. Starting with basic concepts, we also cover advanced analysis techniques and, as an example for a large scale application, demonstrate a complete screen of the Saccharomyces cerevisiae genome. less

关键词： Gene Prediction rna Structure Prediction NCBI BLAST Multiple Sequence Alignment Genome Visualization Database Search Statistical Calculation Programming Language Saccharomyces cerevisiae noncoding rna conserved rna secondary structure

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Angiogenin generates specific stress-induced trna halves and is not involved in tRF-3?mediated gene silencing

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2019年第45期294卷 16930-16941页

作者： Su, Zhangli Kuscu, Canan Malik, Asrar Shibata, Etsuko Dutta, Anindya Univ Virginia Dept Biochem & Mol Genet Charlottesville VA 22901 USA Univ Tennessee Transplant Res Inst Dept Surg Hlth Sci Ctr Memphis TN 38163 USA

trna fragments (tRFs) and trna halves have been implicated in various cellular processes, including gene silencing, translation, stress granule assembly, cell differentiation, retrotransposon activity, symbiosis, apoptosis, and more. Overexpressed angiogenin (ANG) cleaves trna anticodons and produces trna halves similar to those produced in response to stress. However, it is not clear whether endogenous ANG is essential for producing the stress-induced trna halves. It is also not clear whether smaller tRFs are generated from the trna halves. Here, using global short rna-Seq approach, we found that ANG overexpression selectively cleaves a subset of trnas, including trna(Glu), trna(Gly), trna(Lys), trna(Val), trna(His), trna(Asp), and trna(SeC) to produce trna halves and tRF-5s that are 26?30 bases long. Surprisingly, ANG knockout revealed that the majority of stress-induced trna halves, except for the 5? half from trna(HisGTG) and the 3? half from trna(AspGTC), are ANG independent, suggesting there are other rnases that produce trna halves. We also found that the 17?25 bases?long tRF-3s and tRF-5s that could enter into Argonaute complexes are not induced by ANG overexpression, suggesting that they are generated independently from trna halves. Consistent with this, ANG knockout did not decrease tRF-3 levels or gene-silencing activity. We conclude that ANG cleaves specific trnas and is not the only rnase that creates trna halves and that the shorter tRFs are not generated from the trna halves or from independent trna cleavage by ANG.

关键词： rna metabolism rna processing transfer rna (trna) ribonuclease stress angiogenin gene regulation noncoding rna small rna trna fragment

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HOTTIP downregulation reduces neuronal damage and microglial activation in Parkinson's disease cell and mouse models

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Neural Regeneration Research 2022年第4期17卷 887-897页

作者： Peng Lun Tao Ji De-Hong Wan Xia Liu Xiao-Dong Chen Shuai Yu Peng Sun Department of Neurosurgery the Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of Neurosurgery Laiyang People’s HospitalYantaiShandong ProvinceChina Department of Endocrine and Metabolic Diseases the Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Emergency Department the Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding rna,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal ***,its role in Parkinson's disease(PD)remains unclear.1-Methyl-4-phenylpyridium(MPP+)and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)were used to establish PD models in SH-SY5 Y and BV2 cells and in C57 BL/6 male mice,*** vitro,after HOTTIP knockdown by sh-HOTTIP transfection,HOTTIP and FOXO1 overexpression promoted SH-SY5 Y apoptosis,BV2 microglial activation,proinflammatory cytokine expression,and nuclear factor kappa-B and NACHT,LRR and PYD domains-containing protein 3 inflammasome *** of mi R-615-3 p inhibited MPP+-induced neuronal apoptosis and microglial inflammation and ameliorated HOTTIP-and FOXO1-mediated nerve injury and *** vivo,HOTTIP knockdown alleviated motor dysfunction in PD mice and reduced neuronal apoptosis and microglial activation in the substantia *** findings suggest that inhibition of HOTTIP mitigates neuronal apoptosis and microglial activation in PD models by modulating mi R-615-3 p/*** study was approved by the Ethics Review Committee of the Affiliated Hospital of Qingdao University,China(approval ***-2018-042)in June 2018.

关键词： apoptosis inflammation miR-615-3p neuron NLRP3 noncoding rna Parkinson's disease HOTTIP

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