scholarly journals Adaptive evolution at mRNA editing sites in soft-bodied cephalopods

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10456
Author(s):  
Mikhail Moldovan ◽  
Zoe Chervontseva ◽  
Georgii Bazykin ◽  
Mikhail S. Gelfand
Keyword(s):  
Positive Selection ◽  
Rna Editing ◽  
Editing Site ◽  
Mrna Sequence ◽  
Mrna Editing ◽  
General Role ◽  
Study Selection ◽  
Contextual Characteristics ◽  
Editing Level

Background The bulk of variability in mRNA sequence arises due to mutation—change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-transcriptional modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Methods We study selection regimes at coleoid A-to-I editing sites, estimate the prevalence of positive selection, and analyze interdependencies between the editing level and contextual characteristics of editing site. Results Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis, we show that edited adenines are more frequently substituted with guanine, an informational analog of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Our study shows that coleoid editing sites may enhance adaptation, which, together with recent observations on Drosophila and human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.

scholarly journals Adaptive evolution at mRNA editing sites in soft-bodied cephalopods

2020 ◽  
Author(s):  
Mikhail A. Moldovan ◽  
Zoe S. Chervontseva ◽  
Georgii A. Bazykin ◽  
Mikhail S. Gelfand
Keyword(s):  
Molecular Evolution ◽  
Nucleotide Sequence ◽  
Rna Editing ◽  
Dna Sequence ◽  
Mrna Sequence ◽  
Post Translational Modification ◽  
Mrna Editing ◽  
General Role ◽  
Evolutionary Features

AbstractThe bulk of variability in mRNA sequence arises due to mutation – change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-translational modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein. Here, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis and with observations on Drosophila and human editing sites, we show that edited adenines are more frequently substituted with guanine, an informational analogue of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Thus, our study shows that coleoid editing sites may enhance adaptation, which, together with distinct evolutionary features of Drosophila and human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans.

scholarly journals Recognition of RNA Editing Sites Is Directed by Unique Proteins in Chloroplasts: Biochemical Identification of cis-Acting Elements and trans-Acting Factors Involved in RNA Editing in Tobacco and Pea Chloroplasts

2002 ◽  
Vol 22 (19) ◽  
pp. 6726-6734 ◽  
Author(s):  
Tetsuya Miyamoto ◽  
Junichi Obokata ◽  
Masahiro Sugiura
Keyword(s):  
Rna Editing ◽  
Editing Site ◽  
Mrna Editing ◽  
Higher Plant ◽  
In Vitro System ◽  
Cis Acting ◽  
Biochemical Identification ◽  
Editing Activity

ABSTRACT RNA editing in higher-plant chloroplasts involves C-to-U conversions at specific sites. Although in vivo analyses have been performed, little is known about the biochemical aspects of chloroplast editing reactions. Here we improved our original in vitro system and devised a procedure for preparing active chloroplast extracts not only from tobacco plants but also from pea plants. Using our tobacco in vitro system, cis-acting elements were defined for psbE and petB mRNAs. Distinct proteins were found to bind specifically to each cis-element, a 56-kDa protein to the psbE site and a 70-kDa species to the petB site. Pea chloroplasts lack the corresponding editing site in psbE since T is already present in the DNA. Parallel in vitro analyses with tobacco and pea extracts revealed that the pea plant has no editing activity for psbE mRNAs and lacks the 56-kDa protein, whereas petB mRNAs are edited and the 70-kDa protein is also present. Therefore, coevolution of an editing site and its cognate trans-factor was demonstrated biochemically in psbE mRNA editing between tobacco and pea plants.

Genome wide quantification of A-to-I RNA editing activity

2019 ◽  
Author(s):  
Shalom Hillel Roth ◽  
Erez Y. Levanon ◽  
Eli Eisenberg
Keyword(s):  
Rna Editing ◽  
Innate Immune ◽  
Rna Modification ◽  
Immune Disorders ◽  
Computational Tool ◽  
Genome Wide ◽  
Editing Activity ◽  
Single Number ◽  
Editing Level

Abstract Adenosine to inosine (A-to-I) RNA editing by the ADAR enzymes is a common RNA modification, preventing false activation of the innate immune system by endogenous dsRNAs. Methods for quantification of ADAR activity are sought after, due to an increasing interest in the role of ADARs in cancer and auto-immune disorders, as well as attempts to harness the ADAR enzymes for RNA engineering. Here we present the Alu Editing Index (AEI), a robust and simple-to-use computational tool devised for this purpose that produces a single number representing the global editing level from BAM files. The AEI tool is available at https://github.com/a2iEditing/RNAEditingIndexer

scholarly journals A hierarchy in clusters of cephalopod mRNA editing sites

2021 ◽  
Author(s):  
Mikhail A. Moldovan ◽  
Zoe Chervontseva ◽  
Daria Nogina ◽  
Mikhail Gelfand
Keyword(s):  
Rna Editing ◽  
Structural Features ◽  
Editing Site ◽  
Sequence Conservation ◽  
Strong Tendency ◽  
Mrna Editing ◽  
Ideal Object ◽  
Frequent Type ◽  
General Properties

RNA editing in the form of substituting adenine to inosine (A-to-I editing) is the most frequent type of RNA editing, observed in many metazoan species. A-to-I editing sites form clusters in most studied species, and editing at clustered sites depends on editing of the adjacent sites. Although functionally important in some specific cases, A-to-I editing in most considered species is rare, the exception being soft-bodied cephalopods (coleoids), where tens of thousands of potentially important A-to-I editing sites have been identified, making coleoids an ideal object for studying of general properties and evolution of A-to-I editing sites. Here, we apply several diverse techniques to demonstrate a strong tendency of coleoid RNA editing sites to cluster along the transcript. We identify three distinct types of editing site clusters, varying in size, and describe RNA structural features and mechanisms likely underlying formation of these clusters. In particular, these observations may resolve the paradox of sequence conservation at large distances around editing sites.

scholarly journals Landscape of RNA editing reveals new insights into the dynamic gene regulation of spermatogenesis based on integrated RNA-Seq

2018 ◽  
Author(s):  
Xiaodan Wang ◽  
Zhenshuo Zhu ◽  
Xiaolong Wu ◽  
Hao Li ◽  
Tongtong Li ◽  
...  
Keyword(s):  
Rna Editing ◽  
Research Strategy ◽  
Editing Site ◽  
Chromosome 17 ◽  
Rna Seq ◽  
Dynamic Changes ◽  
Coding Regions ◽  
Intergenic Regions ◽  
Important Physiological Process

ABSTRACTSpermatogenesis is an important physiological process associated with male infertility. But whether there are RNA editings (REs) and what’s the role of REs during the process are still unclear. In this study, we integrated published RNA-Seq datasets and established a landscape of REs during the development of mouse spermatogenesis. 7530 editing sites among all types of male germ cells were found, which enrich on some regions of chromosome, including chromosome 17 and both ends of chromosome Y. Totally, REs occur in 2012 genes during spermatogenesis, more than half of which harbor at two different sites of the same gene at least. We also found REs mainly occur in introns, coding regions (CDSs) and intergenic regions. Moreover, about half of the REs in CDSs can cause amino acids changes. Finally, based on our adult male Kunming mice, we verified that there is a non-synonymous A-to-I RNA editing site inCog3during spermatogenesis, which is conserved not only between species but also across tissues. In short, based on the power of integrating RNA-Seq datasets, we provided the landscape of REs and found their dynamic changes during mouse spermatogenesis. This research strategy is general for other types of sequencing datasets and biological problems.

Artificial RNA Editing with ADAR for Gene Therapy

2020 ◽  
Vol 20 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Sonali Bhakta ◽  
Toshifumi Tsukahara
Keyword(s):  
Gene Therapy ◽  
Genetic Code ◽  
Molecular Mechanism ◽  
Rna Editing ◽  
Comparative Studies ◽  
Genetic Diseases ◽  
Adenosine Deaminases ◽  
Family Protein ◽  
Hydrolytic Deamination

Editing mutated genes is a potential way for the treatment of genetic diseases. G-to-A mutations are common in mammals and can be treated by adenosine-to-inosine (A-to-I) editing, a type of substitutional RNA editing. The molecular mechanism of A-to-I editing involves the hydrolytic deamination of adenosine to an inosine base; this reaction is mediated by RNA-specific deaminases, adenosine deaminases acting on RNA (ADARs), family protein. Here, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.

Dissent in the Atlantic World, 1787–1830

2018 ◽  
Author(s):  
Katherine Carté Engel
Keyword(s):  
United States ◽  
African Americans ◽  
First Amendment ◽  
Church And State ◽  
State Level ◽  
The United States ◽  
American Population ◽  
Simple Fact ◽  
General Role

The very term ‘Dissenter’ became problematic in the United States, following the passing of the First Amendment. The formal separation of Church and state embodied in the First Amendment was followed by the ending of state-level tax support for churches. None of the states established after 1792 had formal religious establishments. Baptists, Congregationalists, Presbyterians, and Methodists accounted for the majority of the American population both at the beginning and end of this period, but this simple fact masks an important compositional shift. While the denominations of Old Dissent declined relatively, Methodism grew quickly, representing a third of the population by 1850. Dissenters thus faced several different challenges. Primary among these were how to understand the idea of ‘denomination’ and also the more general role of institutional religion in a post-establishment society. Concerns about missions, and the positions of women and African Americans are best understood within this context.

scholarly journals Role of occupational therapy in musicians’ health: a scoping review protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040922
Author(s):  
Bethany Villas ◽  
Uira Duarte Wisnesky ◽  
Sandra Campbell ◽  
Lauren Slavik ◽  
Amynah S. Mevawala ◽  
...  
Keyword(s):  
Occupational Therapy ◽  
Scoping Review ◽  
Health Conditions ◽  
Study Selection ◽  
Increased Risk ◽  
Scoping Reviews ◽  
Review Protocol ◽  
And Performance ◽  
Meta Analyses

Review question/objectiveThe purpose of this proposed review is twofold: first, to understand the role of occupational therapy presented in the musicians’ health literature; and second, to explore the potential for this role.IntroductionThe intense movement, awkward postures, concentration and emotional communication required of musicians can place them at increased risk of music-related health conditions, such as musculoskeletal disorders and performance anxiety. The development of music-related health conditions can be emotionally and financially devastating. The role of occupational therapy in musicians’ health has been previously discussed; however, no rigorous reviews of the scholarly literature have been published. We will, therefore, undertake a scoping review with the following research questions: (1) what is known about the role of occupational therapy in instrumental musicians’ health? and (2) what is the potential role of occupational therapy in musicians’ health?Methods and analysisA preliminary search of Medline, CINAHL, SCOPUS and Web of Science was previously undertaken by the first author to determine the extent of the research on this topic and to confirm that no other reviews have been conducted or are in progress. Study selection and analysis will follow the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines for conducting a scoping review.Ethics and disseminationFormal ethics approval is not required at our institution for a review of published literature. The results of this review will be shared through peer-reviewed publications, conference presentations and traditional and social media.

scholarly journals Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1): structure–function relationships of RNA editing and dimerization

1999 ◽  
Vol 40 (4) ◽  
pp. 623-635 ◽  
Author(s):  
Ba-Bie Teng ◽  
Scott Ochsner ◽  
Qian Zhang ◽  
Kizhake V. Soman ◽  
Paul P. Lau ◽  
...  
Keyword(s):  
Structure Function ◽  
Rna Editing ◽  
Apolipoprotein B ◽  
Mutational Analysis ◽  
Mrna Editing ◽  
Editing Enzyme

scholarly journals Tethering-induced destabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Atp Binding ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization ◽  
Lateral Sclerosis

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RNA-recognition-motif (RRM) domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), alzheimer's disease (AD) and Multisystem proteinopathy (MSP). Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: (1) upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. (2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity slightly higher to the tethered than isolated forms. (3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1–RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

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