Characterization of the lncRNA transcriptome in mESC-derived motor neurons: Implications for FUS-ALS

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 FUSand TDP-43 or hexanucleotide repeat expansion in C9ORF72 point to the essential role of aberrant RNA metabolismin neurodegeneration. In this study, by taking advantage of an in vitro differentiation system generatingmouse motor neurons (MNs) from embryonic stem cells, we identified and characterized the long non-codingtranscriptome of MNs. Moreover, by using mutant mouse MNs carrying the equivalent of one of the most severeALS-associated FUS alleles (P517L), we identified lncRNAs affected by this mutation. Comparative analysis withhumanMNs derived in vitro frominduced pluripotent stemcells indicated that candidate lncRNAs are conservedbetween mouse and human. Our work provides a global view of the long non-coding transcriptome of MN, as aprerequisite toward the comprehension of the still poorly characterized non-coding side ofMNphysiopathology