Ricerc@Sapienza

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
transcriptome of MNs. Moreover, by using mutant mouse MNs carrying the equivalent of one of the most severe
ALS-associated FUS alleles (P517L), we identified lncRNAs affected by this mutation. Comparative analysis with
humanMNs derived in vitro frominduced pluripotent stemcells indicated that candidate lncRNAs are conserved
between mouse and human. Our work provides a global view of the long non-coding transcriptome of MN, as a
prerequisite toward the comprehension of the still poorly characterized non-coding side ofMNphysiopathology