Faculty Opinions recommendation of Nervous system targets of RNA editing identified by comparative genomics.

Author(s):  
Kelsey Martin
2020 ◽  
Vol 49 (D1) ◽  
pp. D1012-D1019 ◽  
Author(s):  
Luigi Mansi ◽  
Marco Antonio Tangaro ◽  
Claudio Lo Giudice ◽  
Tiziano Flati ◽  
Eli Kopel ◽  
...  

Abstract RNA editing is a relevant epitranscriptome phenomenon able to increase the transcriptome and proteome diversity of eukaryotic organisms. ADAR mediated RNA editing is widespread in humans in which millions of A-to-I changes modify thousands of primary transcripts. RNA editing has pivotal roles in the regulation of gene expression or modulation of the innate immune response or functioning of several neurotransmitter receptors. Massive transcriptome sequencing has fostered the research in this field. Nonetheless, different aspects of the RNA editing biology are still unknown and need to be elucidated. To support the study of A-to-I RNA editing we have updated our REDIportal catalogue raising its content to about 16 millions of events detected in 9642 human RNAseq samples from the GTEx project by using a dedicated pipeline based on the HPC version of the REDItools software. REDIportal now allows searches at sample level, provides overviews of RNA editing profiles per each RNAseq experiment, implements a Gene View module to look at individual events in their genic context and hosts the CLAIRE database. Starting from this novel version, REDIportal will start collecting non-human RNA editing changes for comparative genomics investigations. The database is freely available at http://srv00.recas.ba.infn.it/atlas/index.html.


2007 ◽  
Vol 87 (3) ◽  
pp. 799-823 ◽  
Author(s):  
Mark F. Mehler ◽  
John S. Mattick

The progressive maturation and functional plasticity of the nervous system in health and disease involve a dynamic interplay between the transcriptome and the environment. There is a growing awareness that the previously unexplored molecular and functional interface mediating these complex gene-environmental interactions, particularly in brain, may encompass a sophisticated RNA regulatory network involving the twin processes of RNA editing and multifaceted actions of numerous subclasses of non-protein-coding RNAs. The mature nervous system encompasses a wide range of cell types and interconnections. Long-term changes in the strength of synaptic connections are thought to underlie memory retrieval, formation, stabilization, and effector functions. The evolving nervous system involves numerous developmental transitions, such as neurulation, neural tube patterning, neural stem cell expansion and maintenance, lineage elaboration, differentiation, axonal path finding, and synaptogenesis. Although the molecular bases for these processes are largely unknown, RNA-based epigenetic mechanisms appear to be essential for orchestrating these precise and versatile biological phenomena and in defining the etiology of a spectrum of neurological diseases. The concerted modulation of RNA editing and the selective expression of non-protein-coding RNAs during seminal as well as continuous state transitions may comprise the plastic molecular code needed to couple the intrinsic malleability of neural network connections to evolving environmental influences to establish diverse forms of short- and long-term memory, context-specific behavioral responses, and sophisticated cognitive capacities.


2021 ◽  
Vol 11 (8) ◽  
pp. 1054
Author(s):  
Qin-Wei Wu ◽  
Josef P. Kapfhammer

RNA therapies using RNA editing and interference are currently being developed for neurological diseases. The CRISPR-Cas13 system, based on bacterial enzymes, holds great promise for developing efficient tools for RNA therapies. However, neurotoxic activity has been reported for Cas13a, and recent studies have reported toxic effects of PspCas13b and RfxCas13d during zebrafish and Drosophila embryonic development. It is important to investigate the safety of these bacterial enzymes in the context of the nervous system and neuronal development. In this study, we used mouse cerebellar Purkinje cells as a complex neuron type to test for the potential neurotoxic actions of RfxCas13d and PspCas13b. We found that PspCas13b significantly impeded the dendritic development of cultured Purkinje cells, similar to the neurotoxic action of Cas13a. In contrast, RfxCas13d did not exhibit a significant inhibition of dendritic development. A similar trend was found for axonal outgrowth. These results suggest varying neurotoxic properties for different Cas13 ortholog enzymes. We call for more studies to investigate, and possibly mitigate, the neurotoxicity of Cas13 proteins in order to improve the safety of the CRISPR-Cas13 system for RNA therapies.


2011 ◽  
Vol 9 (2) ◽  
pp. 189-194 ◽  
Author(s):  
James E C Jepson ◽  
Yiannis A Savva ◽  
Kyle A Jay ◽  
Robert A Reenan
Keyword(s):  

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1440
Author(s):  
Michał Zawisza-Álvarez ◽  
Claudia Pérez-Calles ◽  
Giacomo Gattoni ◽  
Jordi Garcia-Fernàndez ◽  
Èlia Benito-Gutiérrez ◽  
...  

RNA editing is a relatively unexplored process in which transcribed RNA is modified at specific nucleotides before translation, adding another level of regulation of gene expression. Cephalopods use it extensively to increase the regulatory complexity of their nervous systems, and mammals use it too, but less prominently. Nevertheless, little is known about the specifics of RNA editing in most of the other clades and the relevance of RNA editing from an evolutionary perspective remains unknown. Here we analyze a key element of the editing machinery, the ADAR (adenosine deaminase acting on RNA) gene family, in an animal with a key phylogenetic position at the root of chordates: the cephalochordate amphioxus. We show, that as in cephalopods, ADAR genes in amphioxus are predominantly expressed in the nervous system; we identify a number of RNA editing events in amphioxus; and we provide a newly developed method to identify RNA editing events in highly polymorphic genomes using orthology as a guide. Overall, our work lays the foundations for future comparative analysis of RNA-editing events across the metazoan tree.


2014 ◽  
Author(s):  
Shahar Alon ◽  
Sandra C Garrett ◽  
Erez Y Levanon ◽  
Sara Olson ◽  
Brenton R Graveley ◽  
...  

2009 ◽  
Vol 2 (1) ◽  
pp. 13 ◽  
Author(s):  
Bao Tan ◽  
Hua Huang ◽  
Runyi Lam ◽  
Tuck Soong

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