A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations
Abstract Background Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the...
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doaj-772a4a2c344547acbbe89129082badc62020-11-25T00:46:09ZengBMCBMC Genomics1471-21642018-01-0119111610.1186/s12864-017-4409-8A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generationsHiba Zaidan0Gokul Ramaswami1Yaela N. Golumbic2Noa Sher3Assaf Malik4Michal Barak5Dalia Galiani6Nava Dekel7Jin B. Li8Inna Gaisler-Salomon9Department of Psychology, University of HaifaDepartment of Genetics, Stanford UniversityFaculty of Education in Technology and Science, TechnionBioinformatics Core Unit, University of HaifaBioinformatics Core Unit, University of HaifaThe Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan UniversityDepartment of Biological Regulation, The Weizmann Institute of ScienceDepartment of Biological Regulation, The Weizmann Institute of ScienceDepartment of Genetics, Stanford UniversityDepartment of Psychology, University of HaifaAbstract Background Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels. Results In agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes. Conclusions Our findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress.http://link.springer.com/article/10.1186/s12864-017-4409-8RNA editingStressTransgenerationalSerotonin receptor 2CRatBrain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiba Zaidan Gokul Ramaswami Yaela N. Golumbic Noa Sher Assaf Malik Michal Barak Dalia Galiani Nava Dekel Jin B. Li Inna Gaisler-Salomon |
spellingShingle |
Hiba Zaidan Gokul Ramaswami Yaela N. Golumbic Noa Sher Assaf Malik Michal Barak Dalia Galiani Nava Dekel Jin B. Li Inna Gaisler-Salomon A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations BMC Genomics RNA editing Stress Transgenerational Serotonin receptor 2C Rat Brain |
author_facet |
Hiba Zaidan Gokul Ramaswami Yaela N. Golumbic Noa Sher Assaf Malik Michal Barak Dalia Galiani Nava Dekel Jin B. Li Inna Gaisler-Salomon |
author_sort |
Hiba Zaidan |
title |
A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations |
title_short |
A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations |
title_full |
A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations |
title_fullStr |
A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations |
title_full_unstemmed |
A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations |
title_sort |
a-to-i rna editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2018-01-01 |
description |
Abstract Background Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels. Results In agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes. Conclusions Our findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress. |
topic |
RNA editing Stress Transgenerational Serotonin receptor 2C Rat Brain |
url |
http://link.springer.com/article/10.1186/s12864-017-4409-8 |
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