MicroRNA Promoter Identification inArabidopsisUsing Multiple Histone Markers

A microRNA is a small noncoding RNA molecule, which functions in RNA silencing and posttranscriptional regulation of gene expression. To understand the mechanism of the activation of microRNA genes, the location of promoter regions driving their expression is required to be annotated precisely. Only a fraction of microRNA genes have confirmed transcription start sites (TSSs), which hinders our understanding of the transcription factor binding events. With the development of the next generation sequencing technology, the chromatin states can be inferred precisely by virtue of a combination of specific histone modifications. Using the genome-wide profiles of nine histone markers including H3K4me2, H3K4me3, H3K9Ac, H3K9me2, H3K18Ac, H3K27me1, H3K27me3, H3K36me2, and H3K36me3, we developed a computational strategy to identify the promoter regions of most microRNA genes inArabidopsis, based upon the assumption that the distribution of histone markers around the TSSs of microRNA genes is similar to the TSSs of protein coding genes. Among 298 miRNA genes, our model identified 42 independent miRNA TSSs and 132 miRNA TSSs, which are located in the promoters of upstream genes. The identification of promoters will provide better understanding of microRNA regulation and can play an important role in the study of diseases at genetic level.

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MicroRNAs in domestic livestock

Physiological Genomics ◽

10.1152/physiolgenomics.00009.2013 ◽

2013 ◽

Vol 45 (16) ◽

pp. 685-696 ◽

Cited By ~ 16

Author(s):

Attia Fatima ◽

Dermot G. Morris

Keyword(s):

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Small Noncoding Rna ◽

Domestic Livestock ◽

Temporal Expression Pattern ◽

Mrna Binding

microRNAs (miRNAs) are a class of small noncoding RNA that bind to complementary sequences in the untranslated regions of multiple target mRNAs resulting in posttranscriptional regulation of gene expression. The recent discovery and expression-profiling studies of miRNAs in domestic livestock have revealed both their tissue-specific and temporal expression pattern. In addition, breed-dependent expression patterns as well as single nucleotide polymorphisms in either the miRNA or in the target mRNA binding site have revealed associations with traits of economic importance and highlight the potential use of miRNAs in future genomic selection programs.

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Polymorphisms in MicroRNA Genes Associated with Schizophrenia Susceptibility but Not with Effectiveness of MECT

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/1959172 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Danwei Zhang ◽

Huihua Li ◽

Kaimo Ding ◽

Zhen Zhang ◽

Si Luo ◽

...

Keyword(s):

Noncoding Rna ◽

Psychiatric Disease ◽

Nucleotide Polymorphisms ◽

Rna Molecules ◽

Small Noncoding Rna ◽

Mirna Genes ◽

Potential Association ◽

Syndrome Scale ◽

Modified Electroconvulsive Therapy ◽

Microrna Genes

Schizophrenia (SCZ) is a common and complex psychiatric disease associated with hereditary and environmental risk factors. MicroRNAs (miRNAs or miRs) are small, noncoding RNA molecules that endogenously regulate gene expression. Single nucleotide polymorphisms (SNPs) in related miRNA genes are associated with susceptibility of the disorder. We wonder if the SNPs have influence on the effectiveness of modified electroconvulsive therapy (MECT) for SCZ. rs1625579 within miR-137, rs6577555 within miR-34, and rs2296616 within miR-107 were sequenced in 150 cases and 150 controls to check the potential association between the SNPs and SCZ. Our results showed that allele G in rs1625579 ( p = 0.005 , adjusted OR = 1.379 , 95 % CI = 1.108 − 1.634 ), allele A in rs6577555 ( p = 0.014 , adjusted OR = 1.246 , 95 % CI = 1.045 − 1.463 ), allele G in rs2296616 ( p < 0.001 , adjusted OR = 1.646 , 95 % CI = 1.374 − 1.879 ) are positively associated with the disorder risk. MECT courses did significantly decrease the level of the miRNAs, except for the variant of rs2296616 with the AA genotype. Schizophrenic phenotypes assessed by the positive and negative syndrome scale (PANSS) were improved after MECT, and there was no significant relevance observed between the effectiveness of MECT and the variants of these loci. Thus, our findings indicate that polymorphisms within the loci may be involved in the pathogenesis of SCZ, and MECT is effective and unbiased for patients harboring different genotypes of the loci.

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The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

Infection and Immunity ◽

10.1128/iai.00345-13 ◽

2013 ◽

Vol 81 (11) ◽

pp. 4081-4090 ◽

Cited By ~ 27

Author(s):

Ilona Bibova ◽

Karolina Skopova ◽

Jiri Masin ◽

Ondrej Cerny ◽

David Hot ◽

...

Keyword(s):

Bordetella Pertussis ◽

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Whooping Cough ◽

Lethal Dose ◽

Rna Chaperone ◽

Content Type ◽

Small Noncoding Rna ◽

Mrna Targets

ABSTRACTBordetella pertussisis a Gram-negative pathogen causing the human respiratory disease called pertussis or whooping cough. Here we examined the role of the RNA chaperone Hfq inB. pertussisvirulence. Hfq mediates interactions between small regulatory RNAs and their mRNA targets and thus plays an important role in posttranscriptional regulation of many cellular processes in bacteria, including production of virulence factors. We characterized anhfqdeletion mutant (Δhfq) ofB. pertussis18323 and show that the Δhfqstrain produces decreased amounts of the adenylate cyclase toxin that plays a central role inB. pertussisvirulence. Production of pertussis toxin and filamentous hemagglutinin was affected to a lesser extent.In vitro, the ability of the Δhfqstrain to survive within macrophages was significantly reduced compared to that of the wild-type (wt) strain. The virulence of the Δhfqstrain in the mouse respiratory model of infection was attenuated, with its capacity to colonize mouse lungs being strongly reduced and its 50% lethal dose value being increased by one order of magnitude over that of the wt strain. In mixed-infection experiments, the Δhfqstrain was then clearly outcompeted by the wt strain. This requirement for Hfq suggests involvement of small noncoding RNA regulation inB. pertussisvirulence.

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Differential Expression of MicroRNAs between Eutopic and Ectopic Endometrium in Ovarian Endometriosis

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/369549 ◽

2010 ◽

Vol 2010 ◽

pp. 1-29 ◽

Cited By ~ 79

Author(s):

Nicoletta Filigheddu ◽

Ilaria Gregnanin ◽

Paolo E. Porporato ◽

Daniela Surico ◽

Beatrice Perego ◽

...

Keyword(s):

Gene Expression ◽

Differential Expression ◽

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Critical Role ◽

Regulation Of Gene Expression ◽

Differentially Expressed ◽

Ovarian Endometriosis ◽

Eutopic Endometrium ◽

Ectopic Endometrium

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identifiedin silicotheir predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopicversuseutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology.

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On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

10.1101/2021.08.01.454607 ◽

2021 ◽

Author(s):

XIang Li ◽

Qiongyi Zhao ◽

Ziqi Wang ◽

Wei-Siang Liau ◽

Dean Basic ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Large Population ◽

Regulation Of Gene Expression ◽

Fear Extinction ◽

Early Gene ◽

Protein Coding ◽

Protein Coding Genes ◽

Chaperone Protein ◽

The Brain

Long-noncoding RNA (lncRNA) comprise a new class of genes that have been assigned key roles in development and disease. Many lncRNAs are specifically transcribed in the brain where they regulate the expression of protein-coding genes that underpin neuronal function; however, their role in learning and memory remains largely unexplored. We used RNA Capture-Seq to identify a large population of lncRNAs that are expressed in the infralimbic cortex of adult male mice in response to fear-related learning, with 14.5% of these annotated in the GENCODE database as lncRNAs with no known function. We combined these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear-extinction learning, and revealed 434 lncRNAs derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discovered an experience-induced lncRNA called ADRAM that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate early gene Nr4a2. This leads to the expulsion of histone deactylases 3 and 4, and the recruitment of the histone acetyltransferase creb binding protein, which drives learning-induced Nr4a2 expression. Knockdown of ADRAM disrupts this interaction, blocks the expression of Nr4a2, and ultimately impairs the formation of fear-extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain, highlights enhancer-derived RNAs (eRNAs) as key players in the epigenetic regulation of gene expression associated with fear extinction, and suggests eRNAs, such as ADRAM, may constitute viable targets in developing novel treatments for fear-related anxiety disorders.

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Translational applications of microRNA genes in medulloblastomas

Clinical & Investigative Medicine ◽

10.25011/cim.v33i4.14225 ◽

2010 ◽

Vol 33 (4) ◽

pp. 223 ◽

Cited By ~ 8

Author(s):

Norbert F Ajeawung ◽

Bin Li ◽

Deepak Kamnasaran

Keyword(s):

Biological Significance ◽

Clinical Importance ◽

Molecular Classification ◽

Qualitative Assessment ◽

Normal Brain ◽

Protein Coding ◽

Rna Molecules ◽

Mirna Genes ◽

Molecular Events ◽

Microrna Genes

Purpose: To provide a critical assessment of the clinical translational applications of microRNA (miRNA) genes in medulloblastomas. Methods: Data were obtained from MEDLINE using Boolean-formatted keyword queries. Top articles were selected for critical analyses - depending on the novelty of findings, qualitative assessment of the citation index and relevance to the diagnosis, prognosis and therapeutic targeting of medulloblastomas. Results: MiRNAs, non-protein-coding RNA molecules, negatively regulate gene expression in a sequence–specific manner during biological processes. In the past few years, miRNA genes have emerged as key regulators of not only molecular events involved in normal brain development and function but also in the molecular pathogenesis of medulloblastomas. In this manner, microRNA genes are identified with functional roles as oncogenes and tumor suppressor genes. At least four miRNAs have proven useful in improving the molecular classification of medulloblastomas, and eight others have shown potential in predicting patients’ overall prognosis. Moreover, more than 10 miRNA genes can be potentially utilized in therapies against medulloblastomas, using nine recent methods of targetting miRNAs. Conclusion: The quest to identify miRNA genes that are of biological significance in medulloblastomas is on an ongoing venture. Most importantly, these miRNAs have been shown to be of clinical importance for improving the accuracy of diagnosis and prognosis and even developing therapies that can significantly improve patients’ overall survival from this deadly disease.

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Computational annotation of miRNA transcription start sites

Briefings in Bioinformatics ◽

10.1093/bib/bbz178 ◽

2020 ◽

Author(s):

Saidi Wang ◽

Amlan Talukder ◽

Mingyu Cha ◽

Xiaoman Li ◽

Haiyan Hu

Keyword(s):

Computational Methods ◽

Large Scale ◽

Transcription Start ◽

Protein Coding ◽

Functional Roles ◽

Transcription Start Sites ◽

Small Noncoding Rnas ◽

Mirna Genes ◽

Genome Wide ◽

Computational Annotation

Abstract Motivation MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in gene regulation and phenotype development. The identification of miRNA transcription start sites (TSSs) is critical to understand the functional roles of miRNA genes and their transcriptional regulation. Unlike protein-coding genes, miRNA TSSs are not directly detectable from conventional RNA-Seq experiments due to miRNA-specific process of biogenesis. In the past decade, large-scale genome-wide TSS-Seq and transcription activation marker profiling data have become available, based on which, many computational methods have been developed. These methods have greatly advanced genome-wide miRNA TSS annotation. Results In this study, we summarized recent computational methods and their results on miRNA TSS annotation. We collected and performed a comparative analysis of miRNA TSS annotations from 14 representative studies. We further compiled a robust set of miRNA TSSs (RSmirT) that are supported by multiple studies. Integrative genomic and epigenomic data analysis on RSmirT revealed the genomic and epigenomic features of miRNA TSSs as well as their relations to protein-coding and long non-coding genes. Contact [email protected], [email protected]

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A new cancer-testis long noncoding RNA, the OTP-AS1 RNA

10.1101/350793 ◽

2018 ◽

Cited By ~ 2

Author(s):

Iuliia K. Karnaukhova ◽

Dmitrii E. Polev ◽

Larisa L. Krukovskaya ◽

Alexey E. Masharsky ◽

Olga V. Nazarenko ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Regulation Of Gene Expression ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Protein Coding ◽

Regulatory Interactions ◽

Normal Tissues ◽

Non Coding Rnas ◽

Cancer Testis

AbstractOrthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are presented by several 300-400 nucleotides long AI267901-like ESTs.We assumed that AI267901-like ESTs belong to longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The found transcript was 2436 nucleotides long polyadenylated sequence in antisense to OTP gene. The corresponding gene consisted of two exons separated by an intron of 2961 bp long. The first exon was found to be 91 bp long and located in the third exon of OTP gene. The second exon was 2345bp long and located in the second intron of OTP gene.The search of possible open reading frames (ORFs) showed the lack of significant ORFs. We have shown the expression of new gene in many human tumors and only in one sampled normal testis. The data suggest that we discovered a new antisense cancer-testis sequence OTP-AS1 (OTP- antisense RNA 1), which belongs to long noncoding RNAs (lncRNAs). According to our findings we assume that OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions.Author summaryPreviously, long non-coding RNAs (lncRNAs) were considered as genetic “noise”. However, it was later shown that only 2% of genomic transcripts have a protein-coding ability. Non-coding RNA is divided into short non-coding RNAs (20-200 nucleotides) and long noncoding RNAs (200-100,000 nucleotides). Genes encoding lncRNA often overlap or are adjacent to protein-coding genes, and localization of this kind is beneficial in order to regulate the transcription of neighboring genes. Studies have shown that of lncRNAs play many roles in the regulation of gene expression. New evidence indicates that dysfunctions of lncRNAs are associated with human diseases and cancer.In our study we found a new cancer-testis long noncoding RNA (OTP-AS1), which is an antisense of protein-coding cancer-testis gene (OTP). Thus, OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. This is supported by the similar profile of their expression. OTP-AS1 may be of interest as a potential diagnostic marker of cancer or a potential target for cancer therapy.Part of OTP-AS1 gene (5’-end of the second exon) is evolutionary younger than the rest of gene sequence and is less conservative. This links OTP-AS1 gene with so-called TSEEN (tumor-specifically expressed, evolutionary novel) genes described by the authors in previous papers.

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NOVOMIR: De Novo Prediction of MicroRNA-Coding Regions in a Single Plant-Genome

Journal of Nucleic Acids ◽

10.4061/2010/495904 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 25

Author(s):

Jan-Hendrik Teune ◽

Gerhard Steger

Keyword(s):

Noncoding Rna ◽

De Novo ◽

Plant Genome ◽

Messenger Rnas ◽

Protein Coding ◽

Rna Molecules ◽

Coding Regions ◽

Mirna Genes ◽

Genomic Scale ◽

Eukaryotic Genomes

MicroRNAs (miRNA) are small regulatory, noncoding RNA molecules that are transcribed as primary miRNAs (pri-miRNA) from eukaryotic genomes. At least in plants, their regulatory activity is mediated through base-pairing with protein-coding messenger RNAs (mRNA) followed by mRNA degradation or translation repression. We describeNOVOMIR, a program for the identification of miRNA genes in plant genomes. It uses a series of filter steps and a statistical model to discriminate a pre-miRNA from other RNAs and does rely neither on prior knowledge of a miRNA target nor on comparative genomics. The sensitivity and specificity ofNOVOMIR for detection of premiRNAs fromArabidopsis thalianais ~0.83 and ~0.99, respectively. Plant pre-miRNAs are more heterogeneous with respect to size and structure than animal pre-miRNAs. Despite these difficulties,NOVOMIR is well suited to perform searches for pre-miRNAs on a genomic scale.NOVOMIR is written in Perl and relies on two additional, free programs for prediction of RNA secondary structure (RNALFOLD, RNASHAPES).

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MicroRNAs in Cardiac Diseases

Cells ◽

10.3390/cells8070737 ◽

2019 ◽

Vol 8 (7) ◽

pp. 737 ◽

Cited By ~ 27

Author(s):

Robin M.W. Colpaert ◽

Martina Calore

Keyword(s):

Cardiac Muscle ◽

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Potential Role ◽

Regulation Of Gene Expression ◽

Cardiac Diseases ◽

Disease Biomarkers ◽

Pathological Conditions ◽

Inherited Cardiomyopathies ◽

Non Coding Rnas

Since their discovery 20 years ago, microRNAs have been related to posttranscriptional regulation of gene expression in major cardiac physiological and pathological processes. We know now that cardiac muscle phenotypes are tightly regulated by multiple noncoding RNA species to maintain cardiac homeostasis. Upon stress or various pathological conditions, this class of non-coding RNAs has been found to modulate different cardiac pathological conditions, such as contractility, arrhythmia, myocardial infarction, hypertrophy, and inherited cardiomyopathies. This review summarizes and updates microRNAs playing a role in the different processes underlying the pathogenic phenotypes of cardiac muscle and highlights their potential role as disease biomarkers and therapeutic targets.

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