Noncoding RNA Scaffolds in Pluripotency

Abstract

### LincRNAs Act in the Circuitry Controlling Pluripotency and Differentiation Guttman et al Nature . 2011;477:295–300. ### Human Long Non-Coding RNAs Promote Pluripotency and Neuronal Differentiation by Association With Chromatin Modifiers and Transcription Factors Ng et al EMBOJ . 2012;31:522–533. The molecular circuitry that maintains pluripotency of mouse and human embryonic stem cells has been protein-centric. Two recent reports now add long noncoding RNAs as partners alongside the transcription factors in the maintenance of pluripotency. Understanding of the biological pathways that maintain pluripotency is one of the most striking developments in modern biology and has the potential to revolutionize the field of regenerative medicine. In the recent past, these pathways have been successfully employed to turn the lineage-committed somatic cell into functional pluripotent stem cell. Until recently research in this area was restricted to protein factors whose role in different biological pathways have been relatively well characterized. Pervasive transcription across mammalian genomes generates thousands of long noncoding transcripts and have been shown to involve diverse biological functions that have impact on development and differentiation. These recent developments generated intense scientific interest in finding new RNAs and mechanisms that could have a potential role in maintaining pluripotency. Previously, small and long RNAs, which are under the control of pluripotent transcription factors, have been implicated in the maintenance of embryonic stem cell (ESC) state and it has been shown that their downregulation promotes ESC differentiation. For example, it has been reported that miRNAs like mir-141, mir-200, and mir-145 regulate the ESC pluripotency program and that their expression is controlled by pluripotent transcription factors like c-Myc and Oct4.1,2 Recent evidence also implicates long noncoding RNAs (lncRNAs), range in size from 200 nt to several hundred kb long in the ESC pluripotency.3 Using custom-designed microarrays, a previous study identified a couple hundred lncRNAs, which are differentially expressed between ESCs and differentiated embryoid bodies. Some of these lncRNAs have been shown to interact with chromatin modifiers and regulate gene expression in cis by controlling local chromatin structure.4 Like small noncoding …