Pseudouridine (Ψ) is the most abundant of >150 nucleoside modifications in RNA. 
Although Ψ was discovered as the first modified nucleoside more than half a 
century ago, neither the enzymatic mechanism of its formation, nor the function 
of this modification are fully elucidated. We present the consistent picture of 
Ψ synthases, their substrates and their substrate positions in model organisms 
of all domains of life as it has emerged to date and point out the challenges 
that remain concerning higher eukaryotes and the elucidation of the enzymatic 
mechanism.