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Grosch, M. ; Rusha, E. ; Ori, C. ; Truong, D.J.J. ; O'Neill, A.C. ; Pertek, A. ; Westmeyer, G.G. ; Drukker, M.

Nucleus size and DNA accessibility are linked to the regulation of paraspeckle formation in cellular differentiation.

BMC Biol. 18:42 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background Many long noncoding RNAs (lncRNAs) have been implicated in general and cell type-specific molecular regulation. Here, we asked what underlies the fundamental basis for the seemingly random appearance of nuclear lncRNA condensates in cells, and we sought compounds that can promote the disintegration of lncRNA condensates in vivo. Results As a basis for comparing lncRNAs and cellular properties among different cell types, we screened lncRNAs in human pluripotent stem cells (hPSCs) that were differentiated to an atlas of cell lineages. We found that paraspeckles, which form by aggregation of the lncRNA NEAT1, are scaled by the size of the nucleus, and that small DNA-binding molecules promote the disintegration of paraspeckles and other lncRNA condensates. Furthermore, we found that paraspeckles regulate the differentiation of hPSCs. Conclusions Positive correlation between the size of the nucleus and the number of paraspeckles exist in numerous types of human cells. The tethering and structure of paraspeckles, as well as other lncRNAs, to the genome can be disrupted by small molecules that intercalate in DNA. The structure-function relationship of lncRNAs that regulates stem cell differentiation is likely to be determined by the dynamics of nucleus size and binding site accessibility.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Long Noncoding Rnas; Pluripotent Stem-cells; Partially Overlapping Sites; Neural Crest; Evolution; Flavopiridol; Chemotherapy; Inhibition; Senescence; Principles
e-ISSN 1741-7007
Journal BMC Biology
Quellenangaben Volume: 18, Issue: 1, Pages: , Article Number: 42 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Research Unit Lung Repair and Regeneration (LRR)
Institute of Biological and Medical Imaging (IBMI)