scholarly journals Rapid and dynamic transcriptome regulation by RNA editing and RNA modifications

2016 ◽  
Vol 213 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Konstantin Licht ◽  
Michael F. Jantsch
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Rna Editing ◽  
Messenger Rna ◽  
Gene Expression Regulation ◽  
Rna Modification ◽  
Rna Modifications ◽  
Transcriptome Regulation ◽  
Affect Gene Expression ◽  
Generation Sequencing

Advances in next-generation sequencing and mass spectrometry have revealed widespread messenger RNA modifications and RNA editing, with dramatic effects on mammalian transcriptomes. Factors introducing, deleting, or interpreting specific modifications have been identified, and analogous with epigenetic terminology, have been designated “writers,” “erasers,” and “readers.” Such modifications in the transcriptome are referred to as epitranscriptomic changes and represent a fascinating new layer of gene expression regulation that has only recently been appreciated. Here, we outline how RNA editing and RNA modification can rapidly affect gene expression, making both processes as well suited to respond to cellular stress and to regulate the transcriptome during development or circadian periods.

scholarly journals Identification and profiling of microRNAs expressed in oral buccal mucosa squamous cell carcinoma of Chinese hamster

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Guo-qiang Xu ◽  
Li-hong Li ◽  
Jia-ning Wei ◽  
Lan-fei Xiao ◽  
Xiao-tang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Expression Regulation ◽  
Chinese Hamster ◽  
Caspase 9 ◽  
Next Generation Sequencing Technology ◽  
Cell Components ◽  
Generation Sequencing

Abstract MicroRNAs are known to play essential role in the gene expression regulation in cancer. In our research, next-generation sequencing technology was applied to explore the abnormal miRNA expression of oral squamous cell carcinoma (OSCC) in Chinese hamster. A total of 3 novel miRNAs (Novel-117, Novel-118, and Novel-135) and 11 known miRNAs (crg-miR-130b-3p, crg-miR-142-5p, crg-miR-21-3p, crg-miR-21-5p, crg-miR-542-3p, crg-miR-486-3p, crg-miR-499-5p, crg-miR-504, crg-miR-34c-5p, crg-miR-34b-5p and crg-miR-34c-3p) were identified. We conducted functional analysis, finding that 340 biological processes, 47 cell components, 46 molecular functions were associated with OSCC. Meanwhile the gene expression of Caspase-9, Caspase-3, Bax, and Bcl-2 were determined by qRT-PCR and the protein expression of PTEN and p-AKT by immunohistochemistry. Our research proposed further insights to the profiles of these miRNAs and provided a basis for investigating the regulatory mechanisms involved in oral cancer research.

scholarly journals Production and Application of Stable Isotope-Labeled Internal Standards for RNA Modification Analysis

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 26 ◽  
Author(s):  
Kayla Borland ◽  
Jan Diesend ◽  
Taku Ito-Kureha ◽  
Vigo Heissmeyer ◽  
Christian Hammann ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Isotope Labeling ◽  
Rna Stability ◽  
Internal Standard ◽  
Modified Nucleosides ◽  
Rna Modification ◽  
Mouse Tissue ◽  
Rna Modifications ◽  
Internal Standards ◽  
Translation Fidelity

Post-transcriptional RNA modifications have been found to be present in a wide variety of organisms and in different types of RNA. Nucleoside modifications are interesting due to their already known roles in translation fidelity, enzyme recognition, disease progression, and RNA stability. In addition, the abundance of modified nucleosides fluctuates based on growth phase, external stress, or possibly other factors not yet explored. With modifications ever changing, a method to determine absolute quantities for multiple nucleoside modifications is required. Here, we report metabolic isotope labeling to produce isotopically labeled internal standards in bacteria and yeast. These can be used for the quantification of 26 different modified nucleosides. We explain in detail how these internal standards are produced and show their mass spectrometric characterization. We apply our internal standards and quantify the modification content of transfer RNA (tRNA) from bacteria and various eukaryotes. We can show that the origin of the internal standard has no impact on the quantification result. Furthermore, we use our internal standard for the quantification of modified nucleosides in mouse tissue messenger RNA (mRNA), where we find different modification profiles in liver and brain tissue.

RNA Modifications in the Central Nervous System

2020 ◽  
Author(s):  
Dan Ohtan Wang
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Gene Expression Regulation ◽  
Spinal Injury ◽  
Regulation Of Gene Expression ◽  
Modified Nucleosides ◽  
Rna Modifications ◽  
The Central Nervous System ◽  
Post Transcriptional Regulation ◽  
The Brain

Epitranscriptomics, a recently emerged field to investigate post-transcriptional regulation of gene expression through enzyme-mediated RNA modifications, is rapidly evolving and integrating with neuroscience. Using a rich repertoire of modified nucleosides and strategically positioning them to the functionally important and evolutionarily conserved regions of the RNA, epitranscriptomics dictates RNA-mediated cell function. The new field is quickly changing our view of the genetic geography in the brain during development and plasticity, impacting major functions from cortical neurogenesis, circadian rhythm, learning and memory, to reward, addiction, stress, stroke, and spinal injury, etc. Thus understanding the molecular components and operational rules of this pathway is becoming a key for us to decipher the genetic code for brain development, function, and disease. What RNA modifications are expressed in the brain? What RNAs carry them and rely on them for function? Are they dynamically regulated? How are they regulated and how do they contribute to gene expression regulation and brain function? This chapter summarizes recent advances that are beginning to answer these questions.

scholarly journals It’s the Little Things (in Viral RNA)

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Jiří František Potužník ◽  
Hana Cahová
Keyword(s):  
Mass Spectrometry ◽  
Viral Rna ◽  
Detection Methods ◽  
Scientific Methodology ◽  
Rna Modifications ◽  
Chemical Modifications ◽  
Viral Protein Synthesis ◽  
Antibody Assays ◽  
Rna Export ◽  
Generation Sequencing

ABSTRACT Chemical modifications of viral RNA are an integral part of the viral life cycle and are present in most classes of viruses. To date, more than 170 RNA modifications have been discovered in all types of cellular RNA. Only a few, however, have been found in viral RNA, and the function of most of these has yet to be elucidated. Those few we have discovered and whose functions we understand have a varied effect on each virus. They facilitate RNA export from the nucleus, aid in viral protein synthesis, recruit host enzymes, and even interact with the host immune machinery. The most common methods for their study are mass spectrometry and antibody assays linked to next-generation sequencing. However, given that the actual amount of modified RNA can be very small, it is important to pair meticulous scientific methodology with the appropriate detection methods and to interpret the results with a grain of salt. Once discovered, RNA modifications enhance our understanding of viruses and present a potential target in combating them. This review provides a summary of the currently known chemical modifications of viral RNA, the effects they have on viral machinery, and the methods used to detect them.

scholarly journals RNA modifications shed new light on DNA's older brother

2017 ◽  
Vol 39 (5) ◽  
pp. 16-19
Author(s):  
Keir H. Murison ◽  
Michelle L. Holland
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Rna Modification ◽  
Stress Adaptation ◽  
Rna Modifications ◽  
Influence Gene Expression

Epigenetics, which literally means ‘on top of genetics’, is a term that describes factors that influence gene expression and are mitotically heritable, but potentially reversible. Recently, N6methyladenosine (m6A) has been identified as a reversible RNA modification that is widespread in mRNA. This is just one of hundreds of modifications to RNA. These exciting findings led to the birth of ‘epitranscriptomics’- the study of reversible RNA modifications. We discuss specific examples of how epigenetic and epitranscriptomic, mechanisms interact to collectively modify genomic output and highlight how these two intertwined forms of gene regulation contribute to homeostasis and stress adaptation.

scholarly journals RNA Editing and Modifications in Mood Disorders

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 872 ◽  
Author(s):  
Alessandro Barbon ◽  
Chiara Magri
Keyword(s):  
Gene Expression ◽  
Rna Editing ◽  
Well Being ◽  
World Health ◽  
Rna Modifications ◽  
Major Health Problem ◽  
Rna Molecules ◽  
The World ◽  
Health Organization

Major depressive disorder (MDD) is a major health problem with significant limitations in functioning and well-being. The World Health Organization (WHO) evaluates MDD as one of the most disabling disorders in the world and with very high social cost. Great attention has been given to the study of the molecular mechanism underpinning MDD at the genetic, epigenetic and proteomic level. However, the importance of RNA modifications has attracted little attention until now in this field. RNA molecules are extensively and dynamically altered by a variety of mechanisms. Similar to “epigenomic” changes, which modify DNA structure or histones, RNA alterations are now termed “epitranscriptomic” changes and have been predicted to have profound consequences for gene expression and cellular functionality. Two of these modifications, adenosine to inosine (A-to-I) RNA editing and m6A methylations, have fascinated researchers over the last years, showing a new level of complexity in gene expression. In this review, we will summary the studies that focus on the role of RNA editing and m6A methylation in MDD, trying to underline their potential breakthroughs and pitfalls.

scholarly journals Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’

Open Biology ◽  
2017 ◽  
Vol 7 (5) ◽  
pp. 170077 ◽  
Author(s):  
Matthias Schaefer ◽  
Utkarsh Kapoor ◽  
Michael F. Jantsch
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Molecular Biology ◽  
Genetic Information ◽  
Biological Function ◽  
Rna Modifications ◽  
Single Nucleotide ◽  
Technological Advances ◽  
Nucleotide Resolution ◽  
Single Nucleotide Resolution

The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications.

scholarly journals Widespread remodeling of the m6A RNA-modification landscape by a viral regulator of RNA processing and export

2021 ◽  
Vol 118 (30) ◽  
pp. e2104805118
Author(s):  
Kalanghad Puthankalam Srinivas ◽  
Daniel P. Depledge ◽  
Jonathan S. Abebe ◽  
Stephen A. Rice ◽  
Ian Mohr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Rna Binding ◽  
Viral Gene Expression ◽  
Rna Modification ◽  
Viral Gene ◽  
Viral Mrnas ◽  
Simplex Virus ◽  
Processing Stability ◽  
Hsv 1

N6-methyladenosine (m6A) is the most abundant internal messenger RNA (mRNA) modification, contributing to the processing, stability, and function of methylated RNAs. Methylation occurs in the nucleus during pre-mRNA synthesis and requires a core methyltransferase complex consisting of METTL3, METTL14, and WTAP. During herpes simplex virus (HSV-1) infection, cellular gene expression is profoundly suppressed, allowing the virus to monopolize the host transcription and translation apparatus and antagonize antiviral responses. The extent to which HSV-1 uses or manipulates the m6A pathway is not known. Here, we show that, in primary fibroblasts, HSV-1 orchestrates a striking redistribution of the nuclear m6A machinery that progresses through the infection cycle. METTL3 and METTL14 are dispersed into the cytoplasm, whereas WTAP remains nuclear. Other regulatory subunits of the methyltransferase complex, along with the nuclear m6A-modified RNA binding protein YTHDC1 and nuclear demethylase ALKBH5, are similarly redistributed. These changes require ICP27, a viral regulator of host mRNA processing that mediates the nucleocytoplasmic export of viral late mRNAs. Viral gene expression is initially reduced by small interfering RNA (siRNA)-mediated inactivation of the m6A methyltransferase but becomes less impacted as the infection advances. Redistribution of the nuclear m6A machinery is accompanied by a wide-scale reduction in the installation of m6A and other RNA modifications on both host and viral mRNAs. These results reveal a far-reaching mechanism by which HSV-1 subverts host gene expression to favor viral replication.

scholarly journals A catalog of cis-regulatory mutations in 12 major cancer types

2019 ◽  
Author(s):  
Zhongshan Cheng ◽  
Michael Vermeulen ◽  
Micheal Rollins-Green ◽  
Brian DeVeale ◽  
Tomas Babak
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Gene Expression Regulation ◽  
Patient Survival ◽  
Chromatin Accessibility ◽  
Regulatory Mutations ◽  
Cancer Types ◽  
Affect Gene Expression

AbstractDespite the recent availability of complete genome sequences of tumors from thousands of patients, isolating disease-causing (driver) non-coding mutations from the plethora of somatic variants is notoriously challenging, and only a handful of validated examples exist. By integrating whole-genome sequencing, gene expression, chromatin accessibility, and genetic data from TCGA, we identified 301 non-coding somatic mutations that affect gene expression in cis. These mutations cluster into 36 hotspot regions with diverse molecular mechanisms of gene expression regulation. We further show that these mutations have hallmark features of noncoding drivers; namely, that they confer a positive selection on growth, functionally disrupt transcription factor binding sites, and contribute to disease progression reflected in decreased overall patient survival.

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