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LncRNA CISTR-ACT regulates cell size in human and mouse by guiding FOSL2.
Katerina Kiriakopulos1,2, Katty Soleimanpour1, Brandon J McMurray1
1Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Nature Communications
|December 15, 2025
Summary
This study reveals how the CISTR-ACT long noncoding RNA (lncRNA) controls cell size using DNA and RNA mechanisms. It influences cell size across species and contributes to disease phenotypes.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Cell size and shape are crucial for organismal function.
- Dysregulated cell morphogenesis is linked to disease, but regulatory mechanisms are unclear.
- CISTR-ACT is a novel long noncoding RNA (lncRNA) associated with red blood cell size and inter-chromosomal interactions.
Purpose of the Study:
- To elucidate the gene-regulatory mechanisms of CISTR-ACT in controlling cell size.
- To investigate both DNA- and RNA-encoded functions of CISTR-ACT.
- To understand CISTR-ACT's role in cell morphogenesis and its contribution to clinical phenotypes.
Main Methods:
- In vitro and in vivo functional dissection of CISTR-ACT.
- Analysis of CISTR-ACT's interaction with transcription factor FOSL2.
- Perturbation studies to assess effects on cell size, morphogenesis, and gene regulation.
Main Results:
- CISTR-ACT regulates cell size across diverse cell types and species through multiple mechanisms.
- CISTR-ACT influences genes within its inter-chromosomal environment in trans.
- CISTR-ACT RNA directly interacts with FOSL2, impacting its chromatin binding and regulating morphogenesis and adhesion genes.
Conclusions:
- CISTR-ACT is a conserved lncRNA with dual DNA- and RNA-based functions in cell size regulation.
- CISTR-ACT's interaction with FOSL2 is critical for its role in cell morphogenesis.
- Understanding CISTR-ACT's mechanisms provides insight into cell size control and associated diseases.
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