Nucleus size and DNA accessibility are linked to the regulation of paraspeckle formation in cellular differentiation
| Autor: | Anna Pertek, Chaido Ori, Micha Drukker, Tobias Greisle, Ejona Rusha, Adam C. O’Neill, Markus Grosch, Sebastian Ittermann, Gil G. Westmeyer, Dong-Jiunn Jeffery Truong |
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| Rok vydání: | 2020 |
| Předmět: |
Pluripotent Stem Cells
Cell type Physiology Cellular differentiation Cell Plant Science Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Structural Biology medicine Humans Induced pluripotent stem cell lcsh:QH301-705.5 Ecology Evolution Behavior and Systematics 030304 developmental biology Cell Nucleus 0303 health sciences RNA Cell Differentiation Paraspeckle DNA Cell Biology Paraspeckles Cell biology medicine.anatomical_structure lcsh:Biology (General) RNA Long Noncoding General Agricultural and Biological Sciences Nucleus 030217 neurology & neurosurgery Research Article Developmental Biology Biotechnology |
| Zdroj: | BMC Biology BMC Biology, Vol 18, Iss 1, Pp 1-19 (2020) |
| ISSN: | 1741-7007 |
| Popis: | 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. Graphical abstract |
| Databáze: | OpenAIRE |
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