Abstract
RNA interference (RNAi) screens have been shown to be valuable to study embryonic stem cell (ESC) self-renewal and they have been successfully applied to identify coding as well as noncoding genes required for maintaining pluripotency. Here, we used an RNAi library targeting >640 long noncoding RNAs (lncRNA) to probe for their role in early cell differentiation. Utilizing a Sox1-GFP ESC reporter cell line, we identified the lncRNA lncR492 as lineage-specific inhibitor of neuroectodermal differentiation. Molecular characterization showed that lncR492 interacts with the mRNA binding protein HuR and facilitates its inhibitory function by activation of Wnt signaling. Thus, lncRNAs modulate the fate decision of pluripotent stem cells.
Highlights
Embryonic stem cells (ESC) are characterized by their ability of long-term self-renewal as well as their potential to differentiate into each cell type of the embryo proper
With a transcript length of >200 nucleotides they are defined as long noncoding RNAs
Sox1-GFP ESCs were cultured in medium supplemented with N2B27+2i+LIF under self-renewing conditions
Summary
Embryonic stem cells (ESC) are characterized by their ability of long-term self-renewal as well as their potential to differentiate into each cell type of the embryo proper. After the first isolation of embryonic stem cells from the mouse blastocyst [1, 2] the research community has achieved a reasonable understanding of the regulatory mechanisms controlling self-renewal of ESC [3]. Among the identified transcripts are RNAs that are transcribed by Polymerase II, usually 5’ capped, polyadenylated and spliced but have little or no protein coding potential [5, 6]. With a transcript length of >200 nucleotides they are defined as long noncoding RNAs (lncRNA). LncRNAs can originate intergenically or are transcribed from a promoter shared with the protein-coding gene. Recent research revealed very diverse mechanisms how lncRNA
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