ArticleNucleic acids research2023
MIRELLA: a mathematical model explains the effect of microRNA-mediated synthetic genes regulation on intracellular resource allocation.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 21 citations in OpenAlex.
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- Messenger RNA-encoded reporters for monitoring cellular stress and bioenergetics.Scientific reports · 2026Article
- Emergence and Tandem Repeat-Mediated Elongation of a Translated De Novo Open Reading Frame in Human Oncogenic RNA Gene VPS9D1-AS1 (MYU).Genome biology and evolution · 2026Article
- In Situ Engineering of Tumor Cells as Self-Sustaining cDC1 Programming Factories for Effective Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- The advantage of periodic over constant signalling in microRNA-mediated regulation.Nucleic acids research · 2025Article
- Computational identification of small molecules for increased gene expression by synthetic circuits in mammalian cells.Nature communications · 2025Article
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.Cell systems · 2025Article
- Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.Journal of biological engineering · 2025Article
- Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells.Nature communications · 2025Article
- A coarse-grained bacterial cell model for resource-aware analysis and design of synthetic gene circuits.Nature communications · 2024Article
- Enhancing circuit stability under growth feedback with supplementary repressive regulation.Nucleic acids research · 2024Article
- Multi-input Drug-Controlled Switches of Mammalian Gene Expression Based on Engineered Nuclear Hormone Receptors.ACS synthetic biology · 2023Article
- Resource-aware construct design in mammalian cells.Nature communications · 2023Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Competition for intracellular resources, also known as gene expression burden, induces coupling between independently co-expressed genes, a detrimental effect on predictability and reliability of gene circuits in mammalian cells. We recently showed that microRNA (miRNA)-mediated target downregulation correlates with the upregulation of a co-expressed gene, and by exploiting miRNAs-based incoherent-feed-forward loops (iFFLs) we stabilise a gene of interest against burden. Considering these findings, we speculate that miRNA-mediated gene downregulation causes cellular resource redistribution. Despite the extensive use of miRNA in synthetic circuits regulation, this indirect effect was never reported before. Here we developed a synthetic genetic system that embeds miRNA regulation, and a mathematical model, MIRELLA, to unravel the miRNA (MI) RolE on intracellular resource aLLocAtion. We report that the link between miRNA-gene downregulation and independent genes upregulation is a result of the concerted action of ribosome redistribution and 'queueing-effect' on the RNA degradation pathway. Taken together, our results provide for the first time insights into the hidden regulatory interaction of miRNA-based synthetic networks, potentially relevant also in endogenous gene regulation. Our observations allow to define rules for complexity- and context-aware design of genetic circuits, in which transgenes co-expression can be modulated by tuning resource availability via number and location of miRNA target sites.
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