FTO: An Emerging Molecular Player in Neuropsychiatric Diseases

Abstract

A myriad of chemical modifications of DNA and histones involved in the epigenetic regulation of neural gene expression have been documented and studied in detail since many years. However, more recently, modifications in RNA and their implications for neural gene functions have been progressively investigated. Of these, the most widely studied is the N⁶-methyladenosine (m⁶A) modification. The discovery of the first m⁶A demethylase, known as the fat, mass and obesity (FTO) associated protein, has further fortified the field of epitranscriptomic regulatory mechanisms, owing to FTO's involvement in several biological processes including brain development and function. Concomitantly, multiple lines of evidence have associated FTO with neuropsychiatric disorders. In this review, we discuss how FTO can exert its effect by acting not only on m⁶A but also on O, N⁶-dimethyladenosine (m⁶A_m) in different types of RNA and potentially influence the development of some major neuropsychiatric diseases.

Keywords: FTO; RNA methylation; epitranscriptomics; m(6)A; neuropsychiatric disorders.