Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-β (TGF-β) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems. BMPs are important in embryogenesis and development, and also in maintenance of adult tissue homeostasis. Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects, highlighting the essential functions of BMPs. In this review, we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development. A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.

N6-methyladenosine (m6A) is a prevalent internal modification in mRNA and non- coding RNA affecting various cellular pathways. Here we report the discovery of two additional modifications, N6-hydroxymethyladenosine (hm6A) and N6- formyladenosine (f6A), in mammalian mRNA. We show that FeII- and α-ketoglutarate (α-KG)-dependent fat mass and obesity associated (FTO) protein oxidizes m6A to generates hm6A as an intermediate modification and f6A as a further oxidized product. hm6A and f6A have half-life times of ~3 h in aqueous solution under physiological relevant conditions, and are present in isolated mRNA from human cells as well as mouse tissues. These previously unknown modifications derived from the prevalent m6A in mRNA, formed through oxidative RNA demethylation, may dynamically modulate RNA-protein interactions to affect gene expression regulation.