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BMC Genomics. 2018 Jan 8;19(1):28. doi: 10.1186/s12864-017-4409-8.

A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations.

Author information

1
Department of Psychology, University of Haifa, Haifa, Israel.
2
Department of Genetics, Stanford University, Stanford, CA, USA.
3
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, Los Angeles, USA.
4
Faculty of Education in Technology and Science, Technion, Haifa, Israel.
5
Faculty of Civil and Environmental Engineering, Technion, Haifa, Israel.
6
Bioinformatics Core Unit, University of Haifa, Haifa, Israel.
7
Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Haifa, Israel.
8
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
9
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
10
Department of Psychology, University of Haifa, Haifa, Israel. igsalomon@psy.haifa.ac.il.

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.

KEYWORDS:

Brain; RNA editing; Rat; Serotonin receptor 2C; Stress; Transgenerational; mmPCR-seq

PMID:
29310578
PMCID:
PMC5759210
DOI:
10.1186/s12864-017-4409-8
[Indexed for MEDLINE]
Free PMC Article

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