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Microrna expression and function in prostate cancer： a review of current knowledge and opportunities for discovery

Asian Journal of Andrology 2016年第4期18卷 559-567页

作者： Binod Kumar Shawn E Lupold The James Buchanan Brady Urological Institute Department of Urology Johns Hopkins School of Medicine Baltimore MD USA.

Micrornas （mirnas） are well-conserved noncoding rnas that broadly regulate gene expression through posttranscriptional silencing of coding genes. Dysregulated mirna expression in prostate and other cancers implicates their role in cancer biology. Moreover, functional studies provide support for the contribution of mirnas to several key pathways in cancer initiation and progression. Comparative analyses of mirna gene expression between malignant and nonmalignant prostate tissues, healthy controls and prostate cancer （PCa） patients, as well as less aggressive versus more aggressive disease indicate that mirnas may be future diagnostic or prognostic biomarkers in tumor tissue, blood, or urine. Further, mirnas may be future therapeutics or therapeutic targets. In this review, we examine the mirnas most commonly observed to be de-regulated in PCa gene expression analyses and review the potential contribution of these mirnas to important pathways in PCa initiation and progression.

关键词： mirna prostate cancer noncoding rna

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The roles of non-coding rnas in Parkinson's disease

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MOLECULAR BIOLOGY REPORTS 2016年第11期43卷 1193-1204页

作者： Majidinia, Maryam Mihanfar, Aynaz Rahbarghazi, Reza Nourazarian, Alireza Bagca, BakiyeGoker Avci, Cigir Biray Tabriz Univ Med Sci Dept Biochem & Clin Labs Fac Med Tabriz Iran Tabriz Univ Med Sci Stem Cell Res Ctr Tabriz Iran Tabriz Univ Med Sci Res Ctr Pharmaceut Nanotechnol Tabriz Iran Ege Univ Dept Med Biol Fac Med Izmir Turkey

Parkinson's disease (PD) is considered as a high prevalence neurodegenerative disorders worldwide. Pathologically, the demise of dopamine-producing cells, in large part due to an abnormal accumulation of the alpha-synuclein in the substantia nigra, is one of the main causes of the disease. Up until now, many de novo investigations have been conducted to disclose the mechanisms underlying in PD. Among them, impacts of non-coding rnas (ncrnas) on the pathogenesis and/or progression of PD need to be highlighted. micrornas (mirnas) and long ncrnas (lncrnas) are more noteworthy in this context. mirnas are small ncrnas (with 18-25 nucleotide in length) that control the expression of multiple genes at post-transcriptional level, while lncrnas have longer size (over 200 nucleotides) and are involved in some key biological processes through various mechanisms. Involvement of mirnas has been well documented in the development of PD, particularly gene expression. Hence, in this current review, we will discuss the impacts of mirnas in regulation of the expression of PD-related genes and the role of lncrnas in the pathogenesis of PD.

关键词： noncoding rna Parkinson' disease Microrna Long non-coding rna

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Global Run-On Sequencing (GRO-Seq)

Global Run-On Sequencing (GRO-Seq)

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作者： Alessandro Gardini

Transcription occurring at gene loci results in accumulation of mature rna molecules (i.e., mrnas) that can be easily assayed by RT-PCR or rna sequencing. However, the steady-state level of rna does not accurately mirror transcriptional activity per se. In fact, rna stability plays a major role in determining the relative abundance of any given rna molecule. Here, I describe a protocol of Nuclear Run-On assay coupled to deep sequencing to assess real-time transcription from engaged rna polymerase. Mapping nascent transcripts at the genome-wide scale provides a reliable measure of transcriptional activity in mammalian cells and delivers a high-resolution map of coding and noncoding transcripts that is especially useful for annotation and quantification of short-lived rna molecules. less

关键词： Deep Sequencing Library Preparation Run-on Sequencing Immunoprecipitation Reverse Transcription PCR rna-seq Run-on Assay PCR rna Immunoprecipitation (RIP) Electrophoresis GRO-seq Homo sapiens Nuclear run-on rna polymerase noncoding rna Transcription initiation Enhancer rna Nascent rna Transcription elongation

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Emerging role of long noncoding rnas in autoimmune diseases

Emerging role of long noncoding RNAs in autoimmune diseases

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2015年度安徽省流行病与卫生统计学学术论坛

作者： Guo-Cui Wu Hai-Feng Pan Rui-Xue Leng De-Guang Wang Xiang-Pei Li Xiao-Mei Li Dong-Qing Ye Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical University Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis Anhui Medical University Department of Nephrology The Second Affiliated Hospital of Anhui Medical University Department of Rheumatology and Immunology Anhui Provincial HospitalAffiliated to Anhui Medical University

Long noncoding rna(lncrna),with size larger than 200 nucleotides,is a new class of noncoding *** evidence has revealed that lnc rnas play a key role in the regulation of immunological functions and ***,we review the recent findings of lnc rna regulation in immune functions and in the development of autoimmunity and autoimmune *** addition,we focus on the involvement of lnc rna regulation in innate and adaptive immune responses,immune cell development,and differential expression of lnc rnas 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).

关键词： lncrna noncoding rna Immune function Autoimmunity Autoimmune disease

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Grad-seq guides the discovery of ProQ as a major small rna-binding protein

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2016年第41期113卷 11591-11596页

作者： Smirnov, Alexandre Foerstner, Konrad U. Holmqvist, Erik Otto, Andreas Guenster, Regina Becher, Doerte Reinhardt, Richard Vogel, Joerg Univ Wurzburg Inst Mol Infect Biol RNA Biol Grp D-97080 Wurzburg Germany Univ Wrzburg Core Unit Syst Med D-97080 Wurzburg Germany Ernst Moritz Arndt Univ Greifswald Inst Microbiol D-17489 Greifswald Germany Max Planck Genome Ctr Cologne Max Planck Inst Plant Breeding Res D-50829 Cologne Germany Univ Wurzburg Res Ctr Infect Dis ZINF D-97070 Wurzburg Germany

The functional annotation of transcriptomes and identification of noncoding rna (ncrna) classes has been greatly facilitated by the advent of next-generation rna sequencing which, by reading the nucleotide order of transcripts, theoretically allows the rapid profiling of all transcripts in a cell. However, primary sequence per se is a poor predictor of function, as ncrnas dramatically vary in length and structure and often lack identifiable motifs. Therefore, to visualize an informative rna landscape of organisms with potentially new rna biology that are emerging from microbiome and environmental studies requires the use of more functionally relevant criteria. One such criterion is the association of rnas with functionally important cognate rna-binding proteins. Here we analyze the full ensemble of cellular rnas using gradient profiling by sequencing (Grad-seq) in the bacterial pathogen Salmonella enterica, partitioning its coding and noncoding transcripts based on their network of rna-protein interactions. In addition to capturing established rna classes based on their biochemical profiles, the Grad-seq approach enabled the discovery of an overlooked large collective of structured small rnas that form stable complexes with the conserved protein ProQ. We show that ProQ is an abundant rna-binding protein with a wide range of ligands and a global influence on Salmonella gene expression. Given its generic ability to chart a functional rna landscape irrespective of transcript length and sequence diversity, Grad-seq promises to define functional rna classes and major rna-binding proteins in both model species and genetically intractable organisms.

关键词： small rna noncoding rna rna-protein interaction ProQ Hfq

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Developmental regulation of X-chromosome inactivation

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SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 2016年 56卷 88-99页

作者： Payer, Bernhard Barcelona Inst Sci & Technol CRG Barcelona 08003 Spain UPF Barcelona 08003 Spain

With the emergence of sex-determination by sex chromosomes, which differ in composition and number between males and females, appeared the need to equalize X-chromosomal gene dosage between the sexes. Mammals have devised the strategy of X-chromosome inactivation (XCI), in which one of the two X-chromosomes is rendered transcriptionally silent in females. In the mouse, the best-studied model organism with respect to XCI, this inactivation process occurs in different forms, imprinted and random, interspersed by periods of X-chromosome reactivation (XCR), which is needed to switch between the different modes of XCI. In this review, I describe the recent advances with respect to the developmental control of XCI and XCR and in particular their link to differentiation and pluripotency. Furthermore, I review the mechanisms, which influence the timing and choice, with which one of the two X-chromosomes is chosen for inactivation during random XCI. This has an impact on how females are mosaics with regard to which X-chromosome is active in different cells, which has implications on the severity of diseases caused by X-linked mutations. (C) 2016 Elsevier Ltd. All rights reserved.

关键词： X-chromosome inactivation Epigenetics Development Reprogramming Pluripotency noncoding rna

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GRO-seq, A Tool for Identification of Transcripts Regulating Gene Expression

GRO-seq, A Tool for Identification of Transcripts Regulating...

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作者： Rui Lopes Reuven Agami Gozde Korkmaz

The advent of next-generation sequencing (NGS) technologies has revolutionized the way we do research on gene expression. High-throughput transcriptomics became possible with the development of microarray technology, but its widespread application only occurred after the emergence of massive parallel sequencing. Especially, rna sequencing (rna-seq) has greatly increased our knowledge about the genome and led to the identification and annotation of novel classes of rnas in different species. However, rna-seq measures the steady-state level of a given rna, which is the equilibrium between transcription, processing, and degradation. In recent years, a number of dedicated rna-seq technologies were developed to measure specifically transcription events. Global run-on sequencing (GRO-seq) is the most widely used method to measure nascent rna, and in recent years, it has been applied successfully to study the function and mechanism of action of noncoding rnas. Here, we describe a detailed protocol of GRO-seq that can be readily applied to investigate different aspects of rna biology in human cells. less

关键词： GRO-seq rna Immunoprecipitation (RIP) PCR Transcriptomics Microarray rna-seq Run-on Sequencing Illumina Sequencing Reverse Transcription PCR Nucleic Acid Microarray Library Preparation DNA Ligation Data analysis TruSeq Nicotiana tabacum Sequencing noncoding rna Enhancer Nascent transcription Anti-BrdU

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Identification of Transcribed Enhancers by Genome-Wide Chromatin Immunoprecipitation Sequencing

Identification of Transcribed Enhancers by Genome-Wide Chrom...

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作者： Steven Blinka Michael H. Reimer Kirthi Pulakanti Luca Pinello Guo-Cheng Yuan Sridhar Rao

Recent work has shown that rna polymerase II-mediated transcription at distal cis-regulatory elements serves as a mark of highly active enhancers. Production of noncoding rnas at enhancers, termed ernas, correlates with higher expression of genes that the enhancer interacts with; hence, ernas provide a new tool to model gene activity in normal and disease tissues. Moreover, this unique class of noncoding rna has diverse roles in transcriptional regulation. Transcribed enhancers can be identified by a common signature of epigenetic marks by overlaying a series of genome-wide chromatin immunoprecipitation and rna sequencing datasets. A computational approach to filter non-enhancer elements and other classes of noncoding rnas is essential to not cloud downstream analysis. Here we present a protocol that combines wet and dry bench methods to accurately identify transcribed enhancers genome-wide as well as an experimental procedure to validate these datasets. less

关键词： ChIP-seq ChIP Assay rna-seq Snap Freeze Sonication Electrophoresis Statistical Calculation Data Mining Library Preparation Bowtie Peak Calling GRO-seq Reverse Osmosis Python Trimmomatic SAMtools bedtools Mus musculus noncoding rna erna ENCODE Global run on sequencing Transcribed enhancer Anti-rabbit

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Regulators in the DNA damage response

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ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 2016年 594卷 18-25页

作者： Liu, Yunhua Li, Yujing Lu, Xiongbin Univ Texas MD Anderson Canc Ctr Dept Canc Biol Unit 19061515 Holcombe Blvd Houston TX 77030 USA

Maintenance of genome integrity is essential for the proper function of all cells and organisms. In response to both endogenous and exogenous DNA damaging agents, mammalian cells have evolved a delicate system to sense DNA damage, stop cell cycle progression, modulate cell metabolism, repair damaged DNA, and induce programmed cell death if the damage is too severe. This coordinated global signaling network, namely the DNA damage response (DDR), ensures the genome stability under DNA damaging stress. A variety of regulators have been shown to modulate the activity and levels of key proteins in the DDR, including kinases, phosphatases, ubiquitin ligases, deubiquitinases, and other protein modifying enzymes. Epigenetic regulators, particularly micrornas and long noncoding rnas, have been emerging as an important payer of regulation in addition to canonical DNA damage signaling proteins. In this review, we will discuss the functional interaction between the regulators and their targets in the DDR. (C) 2016 Elsevier Inc. All rights reserved.

关键词： DNA damage response Posttranslational modification noncoding rna microrna Long noncoding rna

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The Multifarious Hippocampal Functions of Microrna-137

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NEUROSCIENTIST 2016年第5期22卷 440-446页

作者： Kos, Aron Aschrafi, Armaz Kasri, Nael Nadif Radboud Univ Nijmegen Med Ctr Dept Cognit Neurosci Nijmegen Netherlands Donders Inst Brain Cognit & Behav Ctr Neurosci Geert Grootepl 21 NL-6525 AJ Nijmegen Netherlands Radboud Univ Nijmegen Med Ctr Dept Human Genet Nijmegen Netherlands

Micrornas (miRs) have emerged as a powerful class of endogenous noncoding rnas involved in posttranscriptional gene expression regulation. miR-137 has repeatedly been associated with schizophrenia and intellectual disability. Recent studies describe the mechanisms of miR-137 in mediating basic synaptic transmission and plasticity in the hippocampus. A picture is emerging in which miR-137 acts as a potent player in regulating glutamatergic synaptic transmission in the hippocampus by controlling the translation of functionally critical genes at spatially opposite ends of the synapse, contributing to the pathogenesis of cognitive impairments as seen in neurodevelopmental disorders.

关键词： schizophrenia intellectual disability noncoding rna epigenetics trisynaptic loop glutamatergic neurons neurotransmission

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