ArticleScientific reports2017
Optimal Down Regulation of mRNA Translation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 0 citations in OpenAlex.
- Optimization of ribosome utilization inPNAS nexus · 2023Article
- On the gain of entrainment in theJournal of the Royal Society, Interface · 2023Article
- Translation in the cell under fierce competition for shared resources: a mathematical model.Journal of the Royal Society, Interface · 2022Article
- Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes.Journal of the Royal Society, Interface · 2022Article
- Variability in mRNA translation: a random matrix theory approach.Scientific reports · 2021Article
- The developmental-genetics of canalization.Seminars in cell & developmental biology · 2019Review
- Networks of ribosome flow models for modeling and analyzing intracellular traffic.Scientific reports · 2019Article
- Ribosome flow model with extended objects.Journal of the Royal Society, Interface · 2017Article
- Optimal Translation Along a Circular mRNA.Scientific reports · 2017Article
- Article
- A deterministic mathematical model for bidirectional excluded flow with Langmuir kinetics.PloS one · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Down regulation of mRNA translation is an important problem in various bio-medical domains ranging from developing effective medicines for tumors and for viral diseases to developing attenuated virus strains that can be used for vaccination. Here, we study the problem of down regulation of mRNA translation using a mathematical model called the ribosome flow model (RFM). In the RFM, the mRNA molecule is modeled as a chain of n sites. The flow of ribosomes between consecutive sites is regulated by n + 1 transition rates. Given a set of feasible transition rates, that models the outcome of all possible mutations, we consider the problem of maximally down regulating protein production by altering the rates within this set of feasible rates. Under certain conditions on the feasible set, we show that an optimal solution can be determined efficiently. We also rigorously analyze two special cases of the down regulation optimization problem. Our results suggest that one must focus on the position along the mRNA molecule where the transition rate has the strongest effect on the protein production rate. However, this rate is not necessarily the slowest transition rate along the mRNA molecule. We discuss some of the biological implications of these results.
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