Long Noncoding RNA Moderates MicroRNA Activity to Maintain Self-Renewal in Embryonic Stem Cells

Of the thousands of long noncoding RNAs expressed in embryonic stem cells (ESCs), few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency, or the reprogramming of somatic cells to the pluripotent state. In ESCs, Cyrano is a stably expressed long intergenic noncoding RNA with no previously assigned role. Researchers from the University of North Carolina demonstrate that Cyrano contributes to ESC maintenance, as its depletion results in the loss of hallmarks of self-renewal. Delineation of Cyrano’s network through transcriptomics revealed widespread effects on signaling pathways and gene expression networks that contribute to ESC maintenance. Cyrano shares unique sequence complementarity with the differentiation-associated microRNA, mir-7, and mir-7 overexpression reduces expression of a key self-renewal factor to a similar extent as Cyrano knockdown. This suggests that Cyrano functions to restrain the action of mir-7.

Subcellular localization of Cyrano

lncrna

(A) Specificity of the smFISH probe used to detect Cyrano in R1 mouse ES cells. Nuclei are shown in blue (DAPI); Scale bar, 10 μm. (B) Similar subcellular localization of Cyrano is observed by smFISH in ES 2-1 mouse ES cells. Nuclei are shown in blue (DAPI); Scale bar, 10 μm. (C) Immunofluorescence at a position of 5.2μm within an ES cell colony, using a lamin A/C antibody to localize the nuclear periphery, coupled with smFISH and DAPI staining confirmed the presence of smFISH signals (red arrowheads for contrast, left upper panel; white arrowheads, right lower panel) in the nucleus as well as the cytoplasm. (D) 3D reconstruction of nuclear volume only, indicates a fraction of Cyrano molecules localize to the nucleus (white arrowheads); Scale bar, 3 μm.

Smith KN, Starmer J, Miller SC, Sethupathy P, Magnuson T. (2017) Long Noncoding RNA Moderates MicroRNA Activity to Maintain Self-Renewal in Embryonic Stem Cells. Stem Cell Reports [Epub ahead of print]. [article]

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