Ricerc@Sapienza

BICD2 (BICD Cargo Adaptor 2, MIM*609797) mutations are associated with severe prenatal-onset forms of spinal muscular atrophy, lower extremity-predominant 2B (SMALED2B MIM 618291) or milder forms with childhood-onset (SMALED2A MIM 615290). Etiopathogenesis is not fully clarified and a wide spectrum of phenotypic presentations is reported, ranging from extreme prenatal forms with adverse outcome, to slow progressive late-onset forms.

Long non-coding RNAs (lncRNAs) are currently recognized as crucial players in nervous system development,
function and pathology. In Amyotrophic Lateral Sclerosis (ALS), identification of causative mutations in FUS
and TDP-43 or hexanucleotide repeat expansion in C9ORF72 point to the essential role of aberrant RNA metabolism
in neurodegeneration. In this study, by taking advantage of an in vitro differentiation system generating
mouse motor neurons (MNs) from embryonic stem cells, we identified and characterized the long non-coding

Mutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). FUS is a multifunctional protein involved in the
biogenesis and activity of several types of RNAs, and its role in the pathogenesis of ALS may involve both direct effects of
disease-associated mutations through gain- and loss-of-function mechanisms and indirect effects due to the cross talk between
different classes of FUS-dependent RNAs. To explore how FUS mutations impinge on motor neuron-specific RNA-based