m6A Modification in Mammalian Nervous System Development, Functions, Disorders, and Injuries

Abstract

N6-methyladenosine (m6A) modification, as the most prevalent internal modification on mRNA, has been implicated in many biological processes through regulating mRNA metabolism. Given that m6A modification is highly enriched in the mammalian brain, this dynamic modification provides a crucial new layer of epitranscriptomic regulation of the nervous system. Here, in this review, we summarize the recent progress on studies of m6A modification in the mammalian nervous system ranging from neuronal development to basic and advanced brain functions. We also highlight the detailed underlying mechanisms in each process mediated by m6A writers, erasers, and readers. Besides, the involvement of dysregulated m6A modification in neurological disorders and injuries is discussed as well.

The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells

“…The amount of YTHDF2 antibody (Proteintech, 24744–1-AP) and control IgG used for immunoprecipitation is 5 μg, respectively. RIP experimental steps, RNA sample preparation and sequencing, and sequence data analysis followed the procedures reported previously ( Yu et al, 2021a ).…”

“…N 6 -methyladenosine (m 6 A) is the most widely distributed and extensively studied internal modification in mRNA ( Dominissini et al, 2012 ; Meyer et al, 2012 ; Nachtergaele and He, 2018 ). m 6 A modification has been shown to regulate brain development and functions in the nervous system ( Livneh et al, 2020 ; Yu et al, 2021a ). By effectors, most of these studies have focused on its demethylases (‘m 6 A erasers’) and methyltransferases (‘m 6 A writers’).…”

The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells

“…Ythdf2 fl/fl mice were reported previously (Yu et al 2021) . Six3-cre (Furuta et al 2000) , Thy1-GFP (Feng et al 2000) and Rosa26-eYFP (Srinivas et al 2001) mice were from Jackson Laboratory.…”

“…N 6 -methyladenosine (m 6 A) is the most widely distributed and extensively studied internal modification in mRNA (Dominissini et al 2012; Meyer et al 2012; Nachtergaele and He 2018) . m 6 A modification has been shown to regulate brain development and functions in the nervous system (Livneh et al 2020; Yu et al 2021) . By effectors, most of these studies have focused on its demethylases (“m 6 A erasers”) and methyltransferases (“m 6 A writers”).…”

The Role of m6A on Female Reproduction and Fertility: From Gonad Development to Ovarian Aging

“…Currently, m 6 A modification in neuromuscular system development has been clarified in many studies. METTL3/METTL14, ALKBH5, FTO, YTHDF1/2/3 participated in the development, and disorders of nervous system ( Li et al, 2018 ; Yu et al, 2021 ). The silence of FTO disturbed the skeletal muscle differentiation by suppressing mitochondria biogenesis and energy production involved in mTOR-PGC-1a pathway ( Wang et al, 2017 ).…”