title: Intellectual disabilities, neuronal posttranscriptional RNA metabolism, and RNA-binding proteins: three actors for a complex scenario.
abstract: Intellectual disability (ID) is the most frequent cause of serious handicap in children and young adults and interests 2-3% of worldwide population, representing a serious problem from the medical, social, and economic points of view. The causes are very heterogeneous. Genes involved in ID have various functions altering different pathways important in neuronal function. Regulation of mRNA metabolism is particularly important in neurons for synaptic structure and function. Here, we review ID due to alteration of mRNA metabolism. Functional absence of some RNA-binding proteins--namely, FMRP, FMR2P, PQBP1, UFP3B, VCX-A--causes different forms of ID. These proteins are involved in different steps of RNA metabolism and, even if a detailed analysis of their RNA targets has been performed so far only for FMRP, it appears clear that they modulate some aspects (translation, stability, transport, and sublocalization) of a subset of RNAs coding for proteins, whose function must be relevant for neurons. Two other proteins, DYRK1A and CDKL5, involved in Down syndrome and Rett syndrome, respectively, have been shown to have an impact on splicing efficiency of specific mRNAs. Both proteins are kinases and their effect is indirect. Interestingly, both are localized in nuclear speckles, the nuclear domains where splicing factors are assembled, stocked, and recycled and influence their biogenesis and/or their organization.
authors.affiliation: Institute of Molecular and Cellular Pharmacology, CNRS-UMR6097, Université de Nice Sophia-Antipolis,Valbonne, France. bardoni@ipmc.cnrs.fr
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.forename: Sabiha
authors.initials: S
authors.lastname: Abekhoukh
authors.forename: Samantha
authors.initials: S
authors.lastname: Zongaro
authors.forename: Mireille
authors.initials: M
authors.lastname: Melko
mesh_terms: D000328:Adult; D002648:Child; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins