scholarly journals Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders

2020 ◽  
Author(s):  
Yazdan Asgari ◽  
Julian I.T. Heng ◽  
Nigel Lovell ◽  
Alistair R. R. Forrest ◽  
Hamid Alinejad-Rokny
Keyword(s):  
Neurodevelopmental Disorders ◽  
Significant Proportion ◽  
Biological Significance ◽  
Noncoding Rnas ◽  
Enhancer Activity ◽  
Protein Coding ◽  
Gwas Snps ◽  
Number Variation ◽  
Regulatory Functions ◽  
Neurodevelopment Disorders

AbstractNoncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment disorders is poorly understood. In this study, we identified 908 brain-enriched noncoding RNAs comprising at least one nervous system-related eQTL polymorphism that is associated with protein coding genes and also overlap with chromatin states characterised as enhancers. We referred to such noncoding RNAs with putative enhancer activity as brain ‘enhancer-ncRNAs’. By integrating GWAS SNPs and Copy Number Variation (CNV) data from neurodevelopment disorders, we found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTL-associated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. Taken together, we identified 49 novel NDD-associated ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders.

scholarly journals Short-lived long noncoding RNAs as surrogate indicators for chemical stress in HepG2 cells and their degradation by nuclear RNases

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hidenori Tani ◽  
Ayaka Numajiri ◽  
Motohide Aoki ◽  
Tomonari Umemura ◽  
Tetsuya Nakazato
Keyword(s):  
Stress Responses ◽  
Hepg2 Cells ◽  
Noncoding Rnas ◽  
Heavy Metal Stress ◽  
Chemical Exposure ◽  
Long Noncoding Rnas ◽  
Chemical Stress ◽  
Biological Processes ◽  
Protein Coding ◽  
Regulatory Functions

AbstractLong noncoding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length that have been shown to play important roles in various biological processes. The mechanisms underlying the induction of lncRNA expression by chemical exposure remain to be determined. We identified a novel class of short-lived lncRNAs with half-lives (t1/2) ≤4 hours in human HeLa Tet-off cells, which have been suggested to express many lncRNAs with regulatory functions. As they may affect various human biological processes, short-lived lncRNAs may be useful indicators of the degree of stress on chemical exposure. In the present study, we identified four short-lived lncRNAs, designated as OIP5-AS1, FLJ46906, LINC01137, and GABPB1-AS1, which showed significantly upregulated expression following exposure to hydrogen peroxide (oxidative stress), mercury II chloride (heavy metal stress), and etoposide (DNA damage stress) in human HepG2 cells. These lncRNAs may be useful indicators of chemical stress responses. The levels of these lncRNAs in the cells were increased because of chemical stress-induced prolongation of their decay. These lncRNAs were degraded by nuclear RNases, which are components of the exosome and XRN2, and chemical exposure inhibited the RNase activities within the cells.

scholarly journals Conserved regions in long non-coding RNAs contain abundant translation and protein–RNA interaction signatures

2019 ◽  
Vol 1 (1) ◽  
pp. e2-e2 ◽  
Author(s):  
Jorge Ruiz-Orera ◽  
M Mar Albà
Keyword(s):  
Biological Significance ◽  
Ribosome Profiling ◽  
Evolutionary Analysis ◽  
Amino Acid Sequence Level ◽  
Protein Coding ◽  
Conserved Regions ◽  
Non Coding Rnas ◽  
Rna Interaction ◽  
Regulatory Functions ◽  
Sequence Constraints

Abstract The mammalian transcriptome includes thousands of transcripts that do not correspond to annotated protein-coding genes and that are known as long non-coding RNAs (lncRNAs). A handful of lncRNAs have well-characterized regulatory functions but the biological significance of the majority of them is not well understood. LncRNAs that are conserved between mice and humans are likely to be enriched in functional sequences. Here, we investigate the presence of different types of ribosome profiling signatures in lncRNAs and how they relate to sequence conservation. We find that lncRNA-conserved regions contain three times more ORFs with translation evidence than non-conserved ones, and identify nine cases that display significant sequence constraints at the amino acid sequence level. The study also reveals that conserved regions in intergenic lncRNAs are significantly enriched in protein–RNA interaction signatures when compared to non-conserved ones; this includes sites in well-characterized lncRNAs, such as Cyrano, Malat1, Neat1 and Meg3, as well as in tens of lncRNAs of unknown function. This work illustrates how the analysis of ribosome profiling data coupled with evolutionary analysis provides new opportunities to explore the lncRNA functional landscape.

PlncRNADB: A Repository of Plant lncRNAs and lncRNA-RBP Protein Interactions

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Populus Trichocarpa ◽  
Noncoding Rnas ◽  
Reference Database ◽  
Protein Coding ◽  
Arabidopsis Lyrata ◽  
User Friendly

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.

scholarly journals Chromosomal assembly of the nuclear genome of the endosymbiont-bearing trypanosomatid Angomonas deanei

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John W Davey ◽  
Carolina M C Catta-Preta ◽  
Sally James ◽  
Sarah Forrester ◽  
Maria Cristina M Motta ◽  
...  
Keyword(s):  
Chromosome Number ◽  
Noncoding Rnas ◽  
Nuclear Genome ◽  
Supernumerary Chromosome ◽  
Ribosomal Rnas ◽  
Protein Coding ◽  
Transfer Rnas ◽  
Protein Coding Genes ◽  
Oxford Nanopore ◽  
Genome Assemblies

Abstract Angomonas deanei is an endosymbiont-bearing trypanosomatid with several highly fragmented genome assemblies and unknown chromosome number. We present an assembly of the A. deanei nuclear genome based on Oxford Nanopore sequence that resolves into 29 complete or close-to-complete chromosomes. The assembly has several previously unknown special features; it has a supernumerary chromosome, a chromosome with a 340-kb inversion, and there is a translocation between two chromosomes. We also present an updated annotation of the chromosomal genome with 10,365 protein-coding genes, 59 transfer RNAs, 26 ribosomal RNAs, and 62 noncoding RNAs.

scholarly journals Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3951
Author(s):  
Sarva Keihani ◽  
Verena Kluever ◽  
Eugenio F. Fornasiero
Keyword(s):  
Neuronal Differentiation ◽  
Neuronal Excitability ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Regulatory Mechanisms ◽  
Control Robustness ◽  
Living Organisms ◽  
And Function ◽  
Regulatory Functions ◽  
Neuronal Physiology

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

scholarly journals Disrupting upstream translation in mRNAs is associated with human disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David S. M. Lee ◽  
Joseph Park ◽  
Andrew Kromer ◽  
Aris Baras ◽  
Daniel J. Rader ◽  
...  
Keyword(s):  
Protein Expression ◽  
Biological Significance ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Protein Coding ◽  
Stop Codons ◽  
Human Genes ◽  
Strong Negative Selection ◽  
Disease Associations ◽  
Reading Frames

AbstractRibosome-profiling has uncovered pervasive translation in non-canonical open reading frames, however the biological significance of this phenomenon remains unclear. Using genetic variation from 71,702 human genomes, we assess patterns of selection in translated upstream open reading frames (uORFs) in 5’UTRs. We show that uORF variants introducing new stop codons, or strengthening existing stop codons, are under strong negative selection comparable to protein-coding missense variants. Using these variants, we map and validate gene-disease associations in two independent biobanks containing exome sequencing from 10,900 and 32,268 individuals, respectively, and elucidate their impact on protein expression in human cells. Our results suggest translation disrupting mechanisms relating uORF variation to reduced protein expression, and demonstrate that translation at uORFs is genetically constrained in 50% of human genes.

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.

Long Noncoding RNAs and Human Liver Disease

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Johanna K. DiStefano ◽  
Glenn S. Gerhard
Keyword(s):  
Liver Disease ◽  
Biological Significance ◽  
Noncoding Rnas ◽  
Classification Systems ◽  
Long Noncoding Rnas ◽  
Annual Review ◽  
Publication Date ◽  
Cholestatic Liver Disease ◽  
Diverse Range ◽  
Number Of Publications

Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases

2021 ◽  
pp. 107385842110468
Author(s):  
Yuxin Shen ◽  
Zhengyi Huang ◽  
Ruiqing Yang ◽  
Yunlong Chen ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Small Proportion ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Histone Mark ◽  
Brain Diseases ◽  
Enhancer Activity ◽  
Cis Acting ◽  
High Level ◽  
Classification Function

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.

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