A human ESC-based screen identifies a role for the translated lncRNA < i > LINC00261 < /i > in pancreatic endocrine differentiation

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion ofLINC00261 diminishes insulin+ cells, in a manner independent of the nearby TFFOXA2. One-by-one deletion of each ofLINC00261's open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic differentiation and provides a blueprint for dissection of their coding and noncoding roles.
Source: eLife - Category: Biomedical Science Tags: Computational and Systems Biology Developmental Biology Source Type: research