Parameters | Values | Cognate | Near-cognate | Non-cognate |
K | 0.03 | - | - | - |
k1 | - | 140 | 140 | 2000 |
k01 | - | 85 | 85 | - |
k2 | - | 190 | 190 | - |
k02 | - | 0.23 | 80 | - |
k3 | - | 260 | 0.4 | - |
kG | - | 1000 | 1000 | - |
k4 | - | 1000 | 1000 | - |
k5 | - | 1000 | 60 | - |
k7 | - | 60 | 1000 | - |
kp | - | 200 | 200 | - |
kT | - | 20 | 20 | - |
Translation is a central biological process by which proteins are synthesized from genetic information contained within mRNAs. Here, we investigate the kinetics of translation at the molecular level by a stochastic simulation model. The model explicitly includes RNA sequences, ribosome dynamics, the tRNA pool and biochemical reactions involved in the translation elongation. The results show that the translation efficiency is mainly limited by the available ribosome number, translation initiation and the translation elongation time. The elongation time is a log-normal distribution, with the mean and variance determined by the codon saturation and the process of aa-tRNA selection at each codon binding site. Moreover, our simulations show that the translation accuracy exponentially decreases with the sequence length. These results suggest that aa-tRNA competition is crucial for both translation elongation, translation efficiency and the accuracy, which in turn determined the effective protein production rate of correct proteins. Our results improve the dynamical equation of protein production with a delay differential equation that is dependent on sequence information through both the effective production rate and the distribution of elongation time.
Citation: |
Figure 1. Kinetic scheme of RNA translation. Re-drawn from [6]
Figure 2.
Translation kinetics of a single mRNA sequence. (a) Positions of each ribosome on the sequence. (b) Numbers of protein products. The black solid line represents all protein products, and the red dashed line represents the correctly translated proteins (no incorrect amino acid added by near-cognate aa-tRNAs). Here, the sample sequence is the gene YAL003W from the SGD yeast coding sequence, with a sequence length
Figure 3.
Distribution of the elongation time per codon during the translation of YAL003W. All parameters are the same as described in Fig. 2. The red curve is the fit with the normal distribution
Figure 4.
Dependence of the
Figure 5.
Dependence of the elongation time on the available ribosome number
Figure 6.
Dependence of the
Figure 7.
Dependence of translation efficiency on the maximum number of available ribosomes
Figure 8.
Translation kinetics. (a) Translation efficiency versus sequence length for 1000 yeast coding sequences. Red line shows the fitting with
Figure 9.
Sensitivity analysis of translation efficiency. Bars show changes in the logarithm of translation efficiencies induced by changes in a single parameter
Figure 10.
Table 1.
Values of kinetic rate constants (
Parameters | Values | Cognate | Near-cognate | Non-cognate |
K | 0.03 | - | - | - |
k1 | - | 140 | 140 | 2000 |
k01 | - | 85 | 85 | - |
k2 | - | 190 | 190 | - |
k02 | - | 0.23 | 80 | - |
k3 | - | 260 | 0.4 | - |
kG | - | 1000 | 1000 | - |
k4 | - | 1000 | 1000 | - |
k5 | - | 1000 | 60 | - |
k7 | - | 60 | 1000 | - |
kp | - | 200 | 200 | - |
kT | - | 20 | 20 | - |
Table 2. tRNA pool composition (refer to [5,6]). Also refer to [6] for the anti-codons for the tRNAs
tRNA | Molecules/cell | tRNA | Molecules/cell | tRNA | Molecules/cell |
Ala1 | 3250 | His | 639 | Pro3 | 581 |
Ala2 | 617 | Ile1 | 1737 | Sec | 219 |
Arg2 | 4752 | Ile2 | 1737 | Ser1 | 1296 |
Arg3 | 639 | Leu1 | 4470 | Ser2 | 344 |
Arg4 | 867 | Leu2 | 943 | Ser3 | 1408 |
Arg5 | 420 | Leu3 | 666 | Ser5 | 764 |
Asn | 1193 | Leu4 | 1913 | Thr1 | 104 |
Asp1 | 2396 | Leu5 | 1031 | Thr2 | 541 |
Cys | 1587 | Lys | 1924 | Thr3 | 1095 |
Gln1 | 764 | Met f1 | 1211 | Thr4 | 916 |
Gln2 | 881 | Met f2 | 715 | Trp | 943 |
Glu2 | 4717 | Met m | 706 | Tyr1 | 769 |
Gly1 | 1068 | Phe | 1037 | Tyr2 | 1261 |
Gly2 | 1068 | Pro1 | 900 | Val1 | 3840 |
Gly3 | 4359 | Pro2 | 720 | Val2A | 630 |
Val2B | 635 |
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