Amyotrophic lateral sclerosis is a neurodegenerative disease that causes progressive paralysis that is lethal and incurable to date. In this article, we discovered a developmentally critical microRNA cluster, _mir-17~92_, plays a role in the vulnerability of spinal motor neurons and supplementing this microRNA cluster can prolong the life expectancy in a mouse disease model.
In this article, we demonstrated that a long non-coding RNA, _Meg3_, is required to establish the boundary between two genes that mark spinal motor neurons from different body segments. To suppress the expression of caudal genes from expressing in rostral segments, _Meg3_ forms a complex with PRC2 to suppress them, the catalytic complex that marks histone with repressive modificication H3K27me3.