TASEP modelling provides a parsimonious explanation for the ability of a single uORF to derepress translation during the integrated stress response

  1. Dmitry E Andreev
  2. Maxim Arnold
  3. Stephen J Kiniry
  4. Gary Loughran
  5. Audrey M Michel
  6. Dmitrii Rachinskii  Is a corresponding author
  7. Pavel V Baranov  Is a corresponding author
  1. University College Cork, Ireland
  2. Lomonosov Moscow State University, Russia
  3. The University of Texas at Dallas, United States
7 figures and 3 additional files

Figures

ICIER model.

(A) Parameters of the model. The lattice is shown as a black line with the positions of start and stop codons separated by L sites (codons). Scanning ribosomes are blue and elongating are red in …

https://doi.org/10.7554/eLife.32563.002
uORF length (L) influences how the flux of scanning ribosomes changes downstream (rout) in response to lowered ribosome load (rin) due to stress.

Other parameters in the simulations: tε>σ=0; tσ>ε=0.8; mσ=mε=0.3. (A, B) Relative (rout[rin]/rout[rin=0.1]) (A) and absolute (B) changes in the density of ribosomes downstream of a uORF for a range …

https://doi.org/10.7554/eLife.32563.003
The effect the movement rates (mε) for elongating ribosomes on stress resistance.

Other parameters of the simulations tε>σ=0; tσ>ε=0.8; L=100; mσ=0.3. (A, B) Relative (rout[rin]/rout[rin=0.1]) (A) and absolute (B) changes in the density of ribosomes downstream of the uORF for a …

https://doi.org/10.7554/eLife.32563.006
The effect of uORF initiation efficiency (tσ>ε) on stress resistance.

Other parameters of the simulations tε>σ=0; L=100; mσ=0.3; mε=0.3. (A, B) Relative (rout[rin]/rout[rin=0.1]) (A) and absolute (B) changes in the density of ribosomes downstream of a uORF for a range …

https://doi.org/10.7554/eLife.32563.009
The effect of reinitiation downstream of the uORF on stress resistance.

Other parameters of the simulations tε>σ=0; tσ>ε=0.8; L=100; mσ=0.3; mε=0.3. (A, B) Relative (rout[rin]/rout[rin=0.1]) (A) and absolute (B) changes in the density of ribosomes downstream of a uORF …

https://doi.org/10.7554/eLife.32563.014
The effect of the size of scanning ribosomes (Dσ) and probability of spontaneous ribosome dissociation (Pσ) on stress resistance.

Other parameters of the simulations; tσ>ε=0.8; L=100; mσ=0.3; mε=0.3. (A, B) Absolute changes in the density of ribosomes downstream of a uORF under a scenario in which scanning (A) or elongating (B)…

https://doi.org/10.7554/eLife.32563.017
Correlations between translational stress resistance of mRNAs and features in the 5’ leaders of uOFRs for three studies.

(A) uORF length. (B) uORF translation initiation measured as uORF translation efficiency. (C) Ribosome pausing estimated with pause score. Pearson correlation coefficients (r) and Spearman rank …

https://doi.org/10.7554/eLife.32563.022

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