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Cross-Regulation between TDP-43 and Paraspeckles Promotes Pluripotency-Differentiation Transition
Miha Modic1, Markus Grosch2, Gregor Rot3
1Institute of Stem Cell Research, Helmholtz Zentrum München, 85764 Neuherberg, Germany; The Francis Crick Institute, London NW1 1AT, UK; Department for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Molecular Cell
|May 4, 2019
Summary
The RNA-binding protein TDP-43 and long non-coding RNA Neat1 reciprocally regulate each other, controlling cell fate decisions in pluripotent and differentiated cells.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cellular Differentiation
Background:
- RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are crucial for gene expression.
- Their combined roles in cell fate determination remain largely unexplored.
Purpose of the Study:
- To investigate the interplay between the RBP TDP-43 and the lncRNA Neat1 in regulating pluripotency and differentiation.
- To elucidate the mechanisms of their cross-regulation in cell fate decisions.
Main Methods:
- Analysis of TDP-43 and Neat1 expression and activity in pluripotent and differentiated cells.
- Investigating the impact of TDP-43 on Neat1 isoforms and paraspeckle formation.
- Assessing the role of paraspeckles in sequestering RBPs and influencing gene expression.
Main Results:
- TDP-43 and the long Neat1 isoform exhibit reciprocal expression and activity due to cross-regulation.
- TDP-43 represses paraspeckle formation in pluripotent cells by promoting the short Neat1 isoform.
- Paraspeckles sequester TDP-43, promoting differentiation and embryonic patterning in mice.
Conclusions:
- The cross-regulation between TDP-43 and Neat1 is vital for orchestrating gene networks that govern pluripotency and differentiation.
- This interplay is essential for precise control over cell fate decisions.
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