lncRNAMalat1and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation

Abstract

Neurogenesis is a finely tuned process, which depends on the balanced execution of expression programs that regulate cellular differentiation and proliferation. Different molecular players ranging from transcription factors to chromatin modulators control these programs. Adding to the complexity, noncoding (nc)RNAs also take part in this process. Here we analyzed the function of the long noncoding (lnc)RNAMalat1during neural embryonic stem cell (ESC) differentiation. We find that deletion ofMalat1leads to inhibition of proliferation of neural progenitor cells (NPCs). Interestingly, this coincides with an increase in the expression of miR-26 family members miR-26a and miR-26b in differentiating ESCs. Inactivation of miR-26a/b rescues the proliferative phenotype ofMalat1knockout (KO) cells and leads to accelerated neuronal differentiation of compound Malat1KO/mir-26KO ESCs. Together our work identifies a so far unknown interaction betweenMalat1and miR-26 in the regulation of NPC proliferation and neuronal differentiation.