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Long non‐coding RNAs in stem cell pluripotency

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Abstract Pluripotency refers to the self‐renewal of undifferentiated embryonic stem cells (ESCs), and is maintained by a tightly regulated gene regulatory network involving an intricate interplay between transcription factors and their genomic targets, as well as epigenetic processes that influence gene expression. Long non‐coding RNAs (lncRNAs) are newly discovered members of gene regulatory networks that govern a variety of cell functions. Defined as RNA transcripts larger than 200 nucleotides, lncRNAs have little or no protein‐coding capacity and have been shown to act via various mechanisms, and are important in a variety of biological functions. Recent reports have described the discovery of pluripotent lncRNAs involved in the maintenance and induction of stem cell pluripotency. Here, we discuss how lncRNAs may integrate into the pluripotency network, as well as prominent questions in this emerging field. WIREs RNA 2013, 4:121–128. doi: 10.1002/wrna.1146 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Development

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Proposed mechanisms of lncRNAs that maintain pluripotency. (a) Long non‐coding RNAs (lncRNA) behaves as a modular scaffold that brings two protein complexes in close proximity. (a) lncRNA that couples SOX2 and SUZ12 (part of the PRC2 repressive complex) could facilitate the silencing of SOX2‐bound developmental genes. (b) lncRNAs can be transcriptional co‐regulators. SOX2 binds to lncRNAs in embryonic stem cells (ESCs), as well as RNA‐binding proteins such as LIN28 and heterogeneous ribonucleoproteins (hnRNPs), which may be part of the transcriptional activator complex. (c) Competing endogeneous RNAs (ceRNAs) can sequester microRNAs from pluripotency genes that harbor the microRNA recognition sequence, protecting the pluripotency mRNA from degradation. Pseudogenes of pluripotency genes have been proposed to function as ceRNAs. (d) lncRNAs with enhancer‐like properties may also regulate gene expression in cis.

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RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs
RNA in Disease and Development > RNA in Development

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