STAT3 - NORAD lncRNA Interaction in Human Embryonic Stem-Cells

In recent years non-coding RNAs, specifically long non-coding RNAs (lncRNAs) are emerging as important players in transcriptional and post-transcriptional processes. It has been demonstrated that lncRNAs have many different roles in pluripotency and differentiation of human embryonic stem cells (hESCs). Employing an RNA interactome capture experiment, conducted in nuclear extracts from hESCs, we noticed a significant enrichment of proteins involved in transcriptional regulation and chromatin organization, many not known to bind RNAs. Among these proteins, we observed 40 transcription factors (TFs), including key pluripotent factors. To validate these findings and identify the RNA targets, we performed seCLIP for the key pluripotency TF STAT3. Consistent with its known role as TFs, we found that STAT3 interacts with only a small subset of RNAs, showing a highly specific binding pattern. Among the RNA targets, the lncRNA NORAD was specifically associated with STAT3, and this interaction is required for the localization of STAT3 to the nucleus. Overall, our results support the notion that non-coding RNAs can mediate transcriptional regulation via directly binding to transcription factors. We propose that such interactions involving key pluripotent TFs may play critical roles in maintaining pluripotency in hESCs and in differentiation.