RT Journal Article
SR Electronic
T1 Epitranscriptomic Dysregulation in Stress-induced Psychopathologies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.17.431575
DO 10.1101/2021.02.17.431575
A1 Dan Ohtan Wang
A1 Kandarp Joshi
A1 Anand Gururajan
YR 2021
UL http://biorxiv.org/content/early/2021/02/17/2021.02.17.431575.abstract
AB To date, over 100 different chemical modifications to RNA have been identified. Collectively known as the epitranscriptome, these modifications function to regulate RNA stability and as such, represent another mechanistic layer of post-transcriptional gene regulation. N6-methyladenosine (m6A) is the most common RNA modification in the mammalian brain and has been implicated in a number of processes relevant to neurodevelopment, brain function and behaviour. Here, following brief descriptions on epitranscriptomic mechanisms, we will review the literature on the potential functions of the m6A-methylome in fine-tuning gene expression which include prescribing localisation of transcripts in distal compartments as well as interactions with microRNAs and long non-coding RNAs. We will then discuss findings from rodent and human studies for stress-induced disorders - major depression and post-traumatic stress disorder – which support a hypothesis for a dysregulation of the m6A-methylome and the m6A-machinery in the pathophysiology. To support this, we have included a bioinformatic analysis of publicly available single-cell RNA-sequencing and bulk transcriptomics datasets which suggests an altered m6A-methylome as a consequence of dysregulated cell- and regionally-specific expression of key enzymes involved in the ‘writing, reading and erasing’ of m6A. We hope this review will generate further interest in the field of epitranscriptomics, opening up new lines of research into its involvement in psychiatric disorders.Competing Interest StatementThe authors have declared no competing interest.