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The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance

Adriano Biasini, Adam Alexander Thil Smith, Baroj Abdulkarim, Jennifer Yihong Tan, Maria Ferreira da Silva, View ORCID ProfileAna Claudia Marques
doi: https://doi.org/10.1101/848333
Adriano Biasini
1Department of Computational Biology, University of Lausanne, Switzerland
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Adam Alexander Thil Smith
1Department of Computational Biology, University of Lausanne, Switzerland
2Baker Heart & Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3004, Australia
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Baroj Abdulkarim
1Department of Computational Biology, University of Lausanne, Switzerland
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Jennifer Yihong Tan
1Department of Computational Biology, University of Lausanne, Switzerland
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Maria Ferreira da Silva
1Department of Computational Biology, University of Lausanne, Switzerland
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Ana Claudia Marques
1Department of Computational Biology, University of Lausanne, Switzerland
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  • ORCID record for Ana Claudia Marques
  • For correspondence: anaclaudia.marques@unil.ch
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ABSTRACT

Cell cycle progression requires dynamic and tightly-regulated transitions between well-defined cell cycle stages. These transitions are controlled by the interplay of established cell cycle regulators. Changes in the activity of these regulators are thought to underpin differences in cell cycle kinetics between distinct cell types. Here, we investigate whether cell type-specific long intergenic noncoding RNAs (lincRNAs) contribute to embryonic stem cell adaptations, which have been shown to be essential for the maintenance of embryonic stem cell state.

We used single cell RNA-sequencing data of mouse embryonic stem cells (mESC) staged as G1, S, or G2/M to identify genes differentially expressed between these phases. We found differentially expressed lincRNAs to be enriched amongst cell cycle regulated genes. These cell cycle associated lincRNAs (CC-lincRNAs) are co-expressed with protein-coding genes with established roles in cell cycle progression. Interestingly, 70% of CC-lincRNAs are differentially expressed between G1 and S, suggesting they may contribute to the maintenance of the short G1 phase that characterizes the embryonic stem cell cycle. Consistent with this hypothesis, the promoters of CC-lincRNAs are enriched in pluripotency transcription factor binding sites, and their transcripts are frequently co-regulated with genes involved in the maintenance of pluripotency. We tested the impact of 2 CC-lincRNA candidates and show that modulation of their expression is associated with impaired cell cycle progression, further underlining the contribution of mESC-specific lincRNAs to cell cycle modulation in these cells.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 20, 2019.
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The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance
Adriano Biasini, Adam Alexander Thil Smith, Baroj Abdulkarim, Jennifer Yihong Tan, Maria Ferreira da Silva, Ana Claudia Marques
bioRxiv 848333; doi: https://doi.org/10.1101/848333
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The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance
Adriano Biasini, Adam Alexander Thil Smith, Baroj Abdulkarim, Jennifer Yihong Tan, Maria Ferreira da Silva, Ana Claudia Marques
bioRxiv 848333; doi: https://doi.org/10.1101/848333

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