scholarly journals MicroRNomics: a newly emerging approach for disease biology

2008 ◽  
Vol 33 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Chunxiang Zhang
Keyword(s):  
Gene Expression ◽  
Genomic Medicine ◽  
Noncoding Rnas ◽  
Cellular Tissue ◽  
Tissue Type ◽  
Regulation Of Expression ◽  
Protein Coding ◽  
Small Noncoding Rnas ◽  
Disease Biology ◽  
Genomic Scale

Genomic evidence reveals that gene expression in humans is precisely controlled in cellular, tissue-type, temporal, and condition-specific manners. Completely understanding the regulatory mechanisms of gene expression is therefore one of the most important issues in genomic medicine. Surprisingly, recent analyses of the human and animal genomes have demonstrated that the majority of RNA transcripts are relatively small, noncoding RNAs (sncRNAs), rather than large, protein coding message RNAs (mRNAs). Moreover, these sncRNAs may represent a novel important layer of regulation for gene expression. The most important breakthrough in this new area is the discovery of microRNAs (miRNAs). miRNAs comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. As a group, miRNAs may directly regulate ∼30% of the genes in the human genome. In keeping with the nomenclature of RNomics, which is to study sncRNAs on the genomic scale, “microRNomics” is coined here to describe a novel subdiscipline of genomics that studies the identification, expression, biogenesis, structure, regulation of expression, targets, and biological functions of miRNAs on the genomic scale. A growing body of exciting evidence suggests that miRNAs are important regulators of cell differentiation, proliferation/growth, mobility, and apoptosis. These miRNAs therefore play important roles in development and physiology. Consequently, dysregulation of miRNA function may lead to human diseases such as cancer, cardiovascular disease, liver disease, immune dysfunction, and metabolic disorders. microRNomics may be a newly emerging approach for human disease biology.

Long Noncoding RNAs in Plants

2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Andrzej T. Wierzbicki ◽  
Todd Blevins ◽  
Szymon Swiezewski
Keyword(s):  
Gene Expression ◽  
Nuclear Dna ◽  
Noncoding Rnas ◽  
Chromatin Accessibility ◽  
Long Noncoding Rnas ◽  
Annual Review ◽  
Publication Date ◽  
Protein Coding ◽  
Ribonucleic Acids ◽  
Coding Potential

Plants have an extraordinary diversity of transcription machineries, including five nuclear DNA-dependent RNA polymerases. Four of these enzymes are dedicated to the production of long noncoding RNAs (lncRNAs), which are ribonucleic acids with functions independent of their protein-coding potential. lncRNAs display a broad range of lengths and structures, but they are distinct from the small RNA guides of RNA interference (RNAi) pathways. lncRNAs frequently serve as structural, catalytic, or regulatory molecules for gene expression. They can affect all elements of genes, including promoters, untranslated regions, exons, introns, and terminators, controlling gene expression at various levels, including modifying chromatin accessibility, transcription, splicing, and translation. Certain lncRNAs protect genome integrity, while others respond to environmental cues like temperature, drought, nutrients, and pathogens. In this review, we explain the challenge of defining lncRNAs, introduce the machineries responsible for their production, and organize this knowledge by viewing the functions of lncRNAs throughout the structure of a typical plant gene. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Varicella-Zoster Virus (VZV) Small Noncoding RNAs Antisense to the VZV Latency-Encoded Transcript VLT Enhance Viral Replication

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Punam Bisht ◽  
Biswajit Das ◽  
Paul R. Kinchington ◽  
Ronald S. Goldstein
Keyword(s):  
Gene Expression ◽  
Herpes Zoster ◽  
Varicella Zoster Virus ◽  
Noncoding Rnas ◽  
Human Herpesvirus ◽  
Varicella Zoster ◽  
Small Noncoding Rnas ◽  
Viral Spread ◽  
Additional Layer ◽  
Virally Encoded

ABSTRACT Small noncoding RNAs (sncRNA), including microRNA (miR), are expressed by many viruses to provide an additional layer of gene expression regulation. Our work has shown that varicella-zoster virus (VZV; also called human herpesvirus 3 [HHV3]), the human alphaherpesvirus causing varicella and herpes zoster, expresses 24 virally encoded sncRNA (VZVsncRNA) in infected cells. Here, we demonstrate that several VZVsncRNA can modulate VZV growth, including four VZVsncRNA (VZVsncRNA10, -11, -12, and -13) that are antisense to VLT, a transcript made in lytic infections and associated with VZV latency. The influence on productive VZV growth and spread was assessed in epithelial cells transfected with locked nucleotide analog antagonists (LNAA). LNAA to the four VZVsncRNA antisense to VLT significantly reduced viral spread and progeny titers of infectious virus, suggesting that these sncRNA promoted lytic infection. The LNAA to VZVsncRNA12, encoded in the leader to ORF61, also significantly increased the levels of VLT transcripts. Conversely, overexpression of VZVsncRNA13 using adeno-associated virus consistently increased VZV spread and progeny titers. These results suggest that sncRNA antisense to VZV may regulate VZV growth, possibly by affecting VLT expression. Transfection of LNAA to VZVsncRNA14 and VZVsncRNA9 decreased and increased VZV growth, respectively, while LNAA to three other VZVsncRNA had no significant effects on replication. These data strongly support the conclusion that VZV replication is modulated by multiple virally encoded sncRNA, revealing an additional layer of complexity of VZV regulation of lytic infections. This may inform the development of novel anti-sncRNA-based therapies for treatment of VZV diseases. IMPORTANCE Varicella-zoster virus (VZV) causes herpes zoster, a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNA) are recognized as important actors in modulating gene expression. This study extends our previous work and shows that four VZVsncRNA clustering in and near ORF61 and antisense to the latency-associated transcript of VZV can positively influence productive VZV infection. The ability of multiple exogenous small oligonucleotides targeting VZVsncRNA to inhibit VZV replication strengthens the possibility that they may inform development of novel treatments for painful herpes zoster.

scholarly journals MicroRNAs in Platelets: Should I Stay or Should I Go?

Platelets ◽  
2020 ◽  
Author(s):  
Sonia Águila ◽  
Ernesto Cuenca-Zamora ◽  
Constantino Martínez ◽  
Raúl Teruel-Montoya
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Noncoding Rnas ◽  
Signal Transduction Pathway ◽  
Response To Therapy ◽  
Transduction Pathway ◽  
Small Noncoding Rnas ◽  
And Function

In this chapter, we discuss different topics always using the microRNA as the guiding thread of the review. MicroRNAs, member of small noncoding RNAs family, are an important element involved in gene expression. We cover different issues such as their importance in the differentiation and maturation of megakaryocytes (megakaryopoiesis), as well as the role in platelets formation (thrombopoiesis) focusing on the described relationship between miRNA and critical myeloid lineage transcription factors such as RUNX1, chemokines receptors as CRCX4, or central hormones in platelet homeostasis like TPO, as well as its receptor (MPL) and the TPO signal transduction pathway, that is JAK/STAT. In addition to platelet biogenesis, we review the microRNA participation in platelets physiology and function. This review also introduces the use of miRNAs as biomarkers of platelet function since the detection of pathogenic situations or response to therapy using these noncoding RNAs is getting increasing interest in disease management. Finally, this chapter describes the participation of platelets in cellular interplay, since extracellular vesicles have been demonstrated to have the ability to deliver microRNAs to others cells, modulating their function through intercellular communication, redefining the extracellular vesicles from the so-called “platelet dust” to become mediators of intercellular communication.

scholarly journals Bacterial Noncoding RNAs Excised from within Protein-Coding Transcripts

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Daniel Dar ◽  
Rotem Sorek
Keyword(s):  
Expression Patterns ◽  
Noncoding Rnas ◽  
Large Set ◽  
Rna Structures ◽  
Protein Coding ◽  
Small Noncoding Rnas ◽  
Coding Regions ◽  
Protein Coding Genes ◽  
Evolutionarily Conserved ◽  
Intergenic Regions

ABSTRACT Prokaryotic genomes encode a plethora of small noncoding RNAs (ncRNAs) that fine-tune the expression of specific genes. The vast majority of known bacterial ncRNAs are encoded from within intergenic regions, where their expression is controlled by promoter and terminator elements, similarly to protein-coding genes. In addition, recent studies have shown that functional ncRNAs can also be derived from gene 3′ untranslated regions (3′UTRs) via an alternative biogenesis pathway, in which the ncRNA segment is separated from the mRNA via RNase cleavage. Here, we report the detection of a large set of decay-generated noncoding RNAs (decRNAs), many of which are completely embedded within protein-coding mRNA regions rather than in the UTRs. We show that these decRNAs are “carved out” of the mRNA through the action of RNase E and that they are predicted to fold into highly stable RNA structures, similar to those of known ncRNAs. A subset of these decRNAs is predicted to interact with Hfq or ProQ or both, which act as ncRNA chaperones, and some decRNAs display evolutionarily conserved sequences and conserved expression patterns between different species. These results suggest that mRNA protein-coding regions may harbor a large set of potentially functional small RNAs. IMPORTANCE Bacteria and archaea utilize regulatory small noncoding RNAs (ncRNAs) to control the expression of specific genetic programs. These ncRNAs are almost exclusively encoded within intergenic regions and are independently transcribed. Here, we report on a large set ncRNAs that are “carved out” from within the protein-coding regions of Escherichia coli mRNAs by cellular RNases. These protected mRNA fragments fold into energetically stable RNA structures, reminiscent of those of intergenic regulatory ncRNAs. In addition, a subset of these ncRNAs coprecipitate with the major ncRNA chaperones Hfq and ProQ and display evolutionarily conserved sequences and conserved expression patterns between different bacterial species. Our data suggest that protein-coding genes can potentially act as a reservoir of regulatory ncRNAs.

Long and small noncoding RNAs during oocyte-to-embryo transition in mammals

2017 ◽  
Vol 45 (5) ◽  
pp. 1117-1124 ◽  
Author(s):  
Petr Svoboda
Keyword(s):  
Noncoding Rna ◽  
Transcriptional Control ◽  
Noncoding Rnas ◽  
Rna Degradation ◽  
Early Embryo ◽  
Protein Coding ◽  
Small Noncoding Rnas ◽  
Major Genome ◽  
Silencing Pathways ◽  
And Function

Oocyte-to-embryo transition is a process during which an oocyte ovulates, is fertilized, and becomes a developing embryo. It involves the first major genome reprogramming event in life of an organism where gene expression, which gave rise to a differentiated oocyte, is remodeled in order to establish totipotency in blastomeres of an early embryo. This remodeling involves replacement of maternal RNAs with zygotic RNAs through maternal RNA degradation and zygotic genome activation. This review is focused on expression and function of long noncoding RNAs (lncRNAs) and small RNAs during oocyte-to-embryo transition in mammals. LncRNAs are an assorted rapidly evolving collection of RNAs, which have no apparent protein-coding capacity. Their biogenesis is similar to mRNAs including transcriptional control and post-transcriptional processing. Diverse molecular and biological roles were assigned to lncRNAs although most of them probably did not acquire a detectable biological role. Since some lncRNAs serve as precursors for small noncoding regulatory RNAs in RNA silencing pathways, both types of noncoding RNA are reviewed together.

scholarly journals MICRORNAS WITH SPECIFIC ROLES IN DIABETES AND PSYCHIATRIC DISEASES

2014 ◽  
Vol 87 (2) ◽  
pp. 87-90
Author(s):  
Valentin Rădoi ◽  
Mara Carsote ◽  
Rodica Petriș ◽  
Diana Păun ◽  
Cătălina Poiană
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Mrna Stability ◽  
Noncoding Rnas ◽  
Diabetes Type ◽  
Psychiatric Diseases ◽  
Diabetes Type 1 ◽  
Small Noncoding Rnas ◽  
Human Pathology

Diabetes mellitus is one of the most cited non communicable diseases and the most common metabolic disorder. Epigenetics represents the field of study of heritable changes in gene expression which are not directly related to DNA. Epigenetics is con- cerned, alongside histone modifications, short interfering RNAs etc., with microRNAs (miRNAs) as well. These are small noncoding RNAs, 21 to 23 nucleotides in length, which either inhibit translation or affect mRNA stability and degradation. At present, there are dozens of miRNAs which have been proven to be involved in the animal and human pathology of diabetes (type 1 or 2). This review focuses on the miRNAs which have been identified as playing a role in both psychiatric diseases and diabetes.

scholarly journals Genes for Small, Noncoding RNAs under Sporulation Control in Bacillus subtilis

2006 ◽  
Vol 188 (2) ◽  
pp. 532-541 ◽  
Author(s):  
Jessica M. Silvaggi ◽  
John B. Perkins ◽  
Richard Losick
Keyword(s):  
Bacillus Subtilis ◽  
Sigma Factor ◽  
Transcriptional Profiling ◽  
Noncoding Rnas ◽  
Specific Gene ◽  
Cell Compartment ◽  
Protein Coding ◽  
Small Noncoding Rnas ◽  
Indirect Control ◽  
Intergenic Regions

ABSTRACT The process of sporulation in the bacterium Bacillus subtilis is known to involve the programmed activation of several hundred protein-coding genes. Here we report the discovery of previously unrecognized genes under sporulation control that specify small, non-protein-coding RNAs (sRNAs). Genes for sRNAs were identified by transcriptional profiling with a microarray bearing probes for intergenic regions in the genome and by use of a comparative genomics algorithm that predicts regions of conserved RNA secondary structure. The gene for one such sRNA, SurA, which is located in the region between yndK and yndL, was induced at the start of development under the indirect control of the master regulator for entry into sporulation, Spo0A. The gene for a second sRNA, SurC, located in the region between dnaJ and dnaK, was switched on at a late stage of sporulation by the RNA polymerase sigma factor σK, which directs gene transcription in the mother cell compartment of the developing sporangium. Finally, a third intergenic region, that between polC and ylxS, which specified several sRNAs, including two transcripts produced under the control of the forespore-specific sigma factor σG and a third transcript generated by σK, was identified. Our results indicate that the full repertoire of sporulation-specific gene expression involves the activation of multiple genes for small, noncoding RNAs.

scholarly journals Transcriptome-Wide Identification of Hfq-Associated RNAs in Brucella suis by Deep Sequencing

2015 ◽  
Vol 198 (3) ◽  
pp. 427-435 ◽  
Author(s):  
Bashir Saadeh ◽  
Clayton C. Caswell ◽  
Yanjie Chao ◽  
Philippe Berta ◽  
Alice Rebecca Wattam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Deep Sequencing ◽  
Noncoding Rnas ◽  
Northern Blotting ◽  
Fine Tuning ◽  
Sequencing Analysis ◽  
Control Of Gene Expression ◽  
Content Type ◽  
Small Noncoding Rnas ◽  
Brucella Suis

ABSTRACTRecent breakthroughs in next-generation sequencing technologies have led to the identification of small noncoding RNAs (sRNAs) as a new important class of regulatory molecules. In prokaryotes, sRNAs are often bound to the chaperone protein Hfq, which allows them to interact with their partner mRNA(s). We screened the genome of the zoonotic and human pathogenBrucella suis1330 for the presence of this class of RNAs. We designed a coimmunoprecipitation strategy that relies on the use of Hfq as a bait to enrich the sample with sRNAs and eventually their target mRNAs. By deep sequencing analysis of the Hfq-bound transcripts, we identified a number of mRNAs and 33 sRNA candidates associated with Hfq. The expression of 10 sRNAs in the early stationary growth phase was experimentally confirmed by Northern blotting and/or reverse transcriptase PCR.IMPORTANCEBrucellaorganisms are facultative intracellular pathogens that use stealth strategies to avoid host defenses. Adaptation to the host environment requires tight control of gene expression. Recently, small noncoding RNAs (sRNAs) and the sRNA chaperone Hfq have been shown to play a role in the fine-tuning of gene expression. Here we have used RNA sequencing to identify RNAs associated with theB. suisHfq protein. We have identified a novel list of 33 sRNAs and 62 Hfq-associated mRNAs for future studies aiming to understand the intracellular lifestyle of this pathogen.

scholarly journals SAFB2 enables the processing of suboptimal stem-loop structures in clustered primary miRNA transcripts

2019 ◽  
Author(s):  
Katharina Hutter ◽  
Michael Lohmüller ◽  
Almina Jukic ◽  
Felix Eichin ◽  
Seymen Avci ◽  
...  
Keyword(s):  
Noncoding Rnas ◽  
General Mechanism ◽  
List Type ◽  
Loop Structure ◽  
Stem Loop ◽  
Protein Coding ◽  
Mirna Processing ◽  
Small Noncoding Rnas ◽  
Stem Loop Structure ◽  
Attachment Factor

SummaryMicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally silence most protein-coding genes in mammals. They are generated from primary transcripts containing single or multiple clustered stem-loop structures that are thought to be recognized and cleaved by the DGCR8/DROSHA Microprocessor complex as independent units. Contrasting this view, we here report an unexpected mode of processing of a bicistronic cluster of the miR-15 family, miR-15a-16-1. We find that the primary miR-15a stem-loop is a poor Microprocessor substrate and is consequently not processed on its own, but that the presence of the neighboring primary miR-16-1 stem-loop on the same transcript can compensate for this deficiency in cis. Using a CRISPR/Cas9 screen, we identify SAFB2 (scaffold attachment factor B2) as an essential co-factor in this miR-16-1-assisted pri-miR-15 cleavage, and describe SAFB2 as a novel accessory protein of DROSHA. Notably, SAFB2-mediated cluster assistance expands to other clustered pri-miRNAs including miR-15b, miR-92a and miR-181b, indicating a general mechanism. Together, our study reveals an unrecognized function of SAFB2 in miRNA processing and suggests a scenario in which SAFB2 enables the binding and processing of suboptimal DGCR8/DROSHA substrates in clustered primary miRNA transcripts.Highlightsthe primary miR-15a stem-loop structure per se is a poor Microprocessor substratecleavage of pri-miR-15a requires the processing of an additional miRNA stem-loop on the same RNAsequential pri-miRNA processing or “cluster assistance” is mediated by SAFB proteinsSAFB2 associates with the Microprocessor

Sign in / Sign up

Export Citation Format

Share Document