Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of RNA modifications in brain and behavior.

ABSTRACT: Much progress in our understanding of RNA metabolism has been made since the first RNA nucleoside modification was identified in 1957. Many of these modifications are found in noncoding RNAs but recent interest has focused on coding RNAs. Here, we summarize current knowledge of cellular consequences of RNA modifications, with a special emphasis on neuropsychiatric disorders. We present evidence for the existence of an "RNA code," similar to the histone code, that fine-tunes gene expression in the nervous system by using combinations of different RNA modifications. Unlike the relatively stable genetic code, this combinatorial RNA epigenetic code, or epitranscriptome, may be dynamically reprogrammed as a cause or consequence of psychiatric disorders. We discuss potential mechanisms linking disregulation of the epitranscriptome with brain disorders and identify potential new avenues of research.

SUBMITTER: Jung Y

PROVIDER: S-EPMC6233296 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Role of RNA modifications in brain and behavior.

Jung Y Y Goldman D D

Genes, brain, and behavior 20180301 3

Much progress in our understanding of RNA metabolism has been made since the first RNA nucleoside modification was identified in 1957. Many of these modifications are found in noncoding RNAs but recent interest has focused on coding RNAs. Here, we summarize current knowledge of cellular consequences of RNA modifications, with a special emphasis on neuropsychiatric disorders. We present evidence for the existence of an "RNA code," similar to the histone code, that fine-tunes gene expression in th ...[more]

PMID: 29244246

Similar Datasets

RNA Metabolism Guided by RNA Modifications: The Role of SMUG1 in rRNA Quality Control.

Project description:RNA modifications are essential for proper RNA processing, quality control, and maturation steps. In the last decade, some eukaryotic DNA repair enzymes have been shown to have an ability to recognize and process modified RNA substrates and thereby contribute to RNA surveillance. Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that not only recognizes and removes uracil and oxidized pyrimidines from DNA but is also able to process modified RNA substrates. SMUG1 interacts with the pseudouridine synthase dyskerin (DKC1), an enzyme essential for the correct assembly of small nucleolar ribonucleoproteins (snRNPs) and ribosomal RNA (rRNA) processing. Here, we review rRNA modifications and RNA quality control mechanisms in general and discuss the specific function of SMUG1 in rRNA metabolism. Cells lacking SMUG1 have elevated levels of immature rRNA molecules and accumulation of 5-hydroxymethyluridine (5hmU) in mature rRNA. SMUG1 may be required for post-transcriptional regulation and quality control of rRNAs, partly by regulating rRNA and stability.

| S-EPMC7826747 | biostudies-literature

Assessing the Role of Post-Translational Modifications of Mitochondrial RNA Polymerase

Project description: Not available

| S-EPMC10671485 | biostudies-literature

ALKBHs-facilitated RNA modifications and de-modifications.

Project description:The AlkB gene that protects E.coli against methylation damage to DNA was identified more than 3 decades ago. 20 years later, the AlkB protein was shown to catalyze repair of methylated DNA base lesions by oxidative demethylation. Two human AlkB homologs were characterized with similar DNA repair activities and seven additional human AlkB homologs were identified based on sequence homology. All these dioxygenases, ALKBH1-8 and FTO, contain a conserved ?-ketoglutarate/iron-dependent domain for methyl modifications and de-modifications. Well-designed research over the last 10 years has identified unforeseen substrate heterogeneity for the AlkB homologs, including novel reversible methyl modifications in RNA. The discoveries of RNA demethylation catalyzed by AlkB family enzymes initiated a new realm of gene expression regulation, although the understanding of precise endogenous activities and roles of these RNA demethylases are still undeveloped. It is worth mentioning that the AlkB mechanism and use of ?-ketoglutarate have also emerged to be essential for many enzymes in epigenetic reprogramming that modify and de-modify methylated bases in DNA and methylated amino acids in histones.

| S-EPMC5120542 | biostudies-literature

The Importance of Being Modified: The Role of RNA Modifications in Translational Fidelity.

Project description:The posttranscriptional modifications of tRNA's anticodon stem and loop (ASL) domain represent a third level, a third code, to the accuracy and efficiency of translating mRNA codons into the correct amino acid sequence of proteins. Modifications of tRNA's ASL domain are enzymatically synthesized and site specifically located at the anticodon wobble position-34 and 3'-adjacent to the anticodon at position-37. Degeneracy of the 64 Universal Genetic Codes and the limitation in the number of tRNA species require some tRNAs to decode more than one codon. The specific modification chemistries and their impact on the tRNA's ASL structure and dynamics enable one tRNA to decode cognate and "wobble codons" or to expand recognition to synonymous codons, all the while maintaining the translational reading frame. Some modified nucleosides' chemistries prestructure tRNA to read the two codons of a specific amino acid that shares a twofold degenerate codon box, and other chemistries allow a different tRNA to respond to all four codons of a fourfold degenerate codon box. Thus, tRNA ASL modifications are critical and mutations in genes for the modification enzymes and tRNA, the consequences of which is a lack of modification, lead to mistranslation and human disease. By optimizing tRNA anticodon chemistries, structure, and dynamics in all organisms, modifications ensure translational fidelity of mRNA transcripts.

| S-EPMC8118379 | biostudies-literature

A distinct brain pathway links viral RNA exposure to sickness behavior.

Project description:Sickness behaviors and metabolic responses to invading pathogens are common to nearly all types of infection. These responses evolved to provide short-term benefit to the host to ward off infection, but impact on quality of life, and when prolonged lead to neurodegeneration, depression, and cachexia. Among the major infectious agents, viruses most frequently enter the brain, resulting in profound neuroinflammation. We sought to define the unique features of the inflammatory response in the brain to these infections. We demonstrate that the molecular pathway defining the central response to dsRNA is distinct from that found in the periphery. The behavioral and physical response to the dsRNA mimetic poly I:C is dependent on signaling via MyD88 when it is delivered centrally, whereas this response is mediated via the TRIF pathway when delivered peripherally. We also define the likely cellular candidates for this MyD88-dependent step. These findings suggest that symptom management is possible without ameliorating protective antiviral immune responses.

| S-EPMC4951726 | biostudies-literature

RNA Modifications in Genomic RNA of Influenza A Virus and the Relationship between RNA Modifications and Viral Infection.

Project description:Recent studies about the transcriptome-wide presence of RNA modifications have revealed their importance in many cellular functions. Nevertheless, information about RNA modifications in viral RNA is scarce, especially for negative-strand RNA viruses. Here we provide a catalog of RNA modifications including m1A, ac4C, m7G, inosine, and pseudouridine on RNA derived from an influenza A virus infected into A549 cells, as studied by RNA immunoprecipitation followed by deep-sequencing. Possible regions with RNA modifications were found in the negative-strand segments of viral genomic RNA. In addition, our analyses of previously published data revealed that the expression levels of the host factors for RNA modifications were affected by an infection with influenza A virus, and some of the host factors likely have a proviral effect. RNA modification is a novel aspect of host-virus interactions leading to the discovery of previously unrecognized viral pathogenicity mechanisms and has the potential to aid the development of novel antivirals.

| S-EPMC8431438 | biostudies-literature

Individual bee brain behavior-age

Project description:This experiment examines gene expression profiles in individual honey bee brains (adult worker Apis mellifera). The purpose is to test whether behavioral phenotype can be predicted by expression profiles in individual brains in a naturalistic context (i.e., colonies in the field). The two behavioral phenotypes examined are 'nurse' and 'forager'. Other factors examined are age, genotype (full-sister group), and colony environment.<br><br> An additional processed data file is available on the FTP site for this experiment.

2011-02-03 | E-MEXP-24 | biostudies-arrayexpress

Interactions between the rabies virus and nicotinic acetylcholine receptors: A potential role in rabies virus induced behavior modifications.

Project description:Rabies causes approximately 60,000 casualties annually and has a case fatality rate approaching 100% once clinical signs occur. The glycoprotein on the surface of the virion is important for the host immune response and facilitates interaction of the virion with host cell receptors. Nicotinic acetylcholine receptors were the first receptors identified as a molecular target for the rabies virus. Additional targets, including neural cell adhesion molecule, p75 neurotrophin receptor, metabotropic glutamate receptor subtype 2, and integrin β1, have been added to the list, all of which can mediate viral entry into the cell. Multiple receptors and different subtypes of nicotinic acetylcholine receptors result in a complex picture of virus-receptor interactions. In addition, some data suggest that the rabies virus glycoprotein inhibits cell signaling events mediated by various nicotinic receptor subtypes that have been implicated in altering behavior in unaffected animals. This review focuses on interactions between the rabies virus glycoprotein and nicotinic receptors and proposes possible functional consequences, including behavioral modifications and therapeutic approaches for future research.

| S-EPMC9450143 | biostudies-literature

Sex-dependent role for EPHB2 in brain development and autism-associated behavior.

Project description:Autism spectrum disorder (ASD) is characterized by impairments in social communication and interaction and restricted, repetitive behaviors. It is frequently associated with comorbidities, such as attention-deficit hyperactivity disorder, altered sensory sensitivity, and intellectual disability. A de novo nonsense mutation in EPHB2 (Q857X) was discovered in a female patient with ASD [13], revealing EPHB2 as a candidate ASD risk gene. EPHB2 is a receptor tyrosine kinase implicated in axon guidance, synaptogenesis, and synaptic plasticity, positioning it as a plausible contributor to the pathophysiology of ASD and related disorders. In this study, we show that the Q857X mutation produced a truncated protein lacking forward signaling and that global disruption of one EphB2 allele (EphB2+/-) in mice produced several behavioral phenotypes reminiscent of ASD and common associated symptoms. EphB2+/- female, but not male, mice displayed increased repetitive behavior, motor hyperactivity, and learning and memory deficits, revealing sex-specific effects of EPHB2 hypofunction. Moreover, we observed a significant increase in the intrinsic excitability, but not excitatory/inhibitory ratio, of motor cortex layer V pyramidal neurons in EphB2+/- female, but not male, mice, suggesting a possible mechanism by which EPHB2 hypofunction may contribute to sex-specific motor-related phenotypes. Together, our findings suggest that EPHB2 hypofunction, particularly in females, is sufficient to produce ASD-associated behaviors and altered cortical functions in mice.

| S-EPMC8429442 | biostudies-literature

Sex-specific role for the long noncoding RNA Pnky in mouse behavior.

Project description:The aberrant expression of specific long noncoding RNAs (lncRNAs) has been associated with cognitive and psychiatric disorders. Although a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few lncRNAs have been shown to underlie animal behavior. Pnky is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that Pnky has sex-specific roles in mouse behavior and that this lncRNA can underlie specific behavior by functioning in trans. Male Pnky-knockout mice have decreased context generalization in a paradigm of associative fear learning and memory. In female Pnky-knockout mice, there is an increase in the acoustic startle response, a behavior that is altered in affective disorders. Remarkably, expression of Pnky from a bacterial artificial chromosome transgene decreases the acoustic startle response in female Pnky-knockout mice, demonstrating that Pnky can modulate specific animal behavior by functioning in trans. More broadly, these studies illustrate how specific lncRNAs can underlie cognitive and mood disorders.

| S-EPMC11319455 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data