The eutherian-specific SNORD116 family of repeated box C/D
snoRNA genes is suspected to play a major role in the
Prader-Willi syndrome (PWS), yet its molecular function remains poorly understood. Here, we combined phylogenetic and molecular analyses to identify candidate
RNA targets. Based on the analysis of several eutherian orthologs, we found evidence of extensive birth-and-death and conversion events during SNORD116 gene history. However, the consequences for phylogenetic conservation were heterogeneous along the gene sequence. The standard
snoRNA elements necessary for RNA stability and association with dedicated core
proteins were the most conserved, in agreement with the hypothesis that SNORD116 generate genuine snoRNAs. In addition, one of the two antisense elements typically involved in
RNA target recognition was largely dominated by a unique sequence present in at least one subset of gene paralogs in most species, likely the result of a selective effect. In agreement with a functional role, this ASE exhibited a hybridization capacity with putative
mRNA targets that was strongly conserved in eutherians. Moreover, transient downregulation experiments in human cells showed that Snord116 controls the expression and splicing levels of these mRNAs. The functions of two of them,
diacylglycerol kinase kappa and
Neuroligin 3, extend the description of the molecular bases of PWS and reveal unexpected molecular links with the
Fragile X syndrome and
autism spectrum disorders.