December 3rd
Recent Publications Harnessing the Power of Translatomics.
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers, Mukai et al. investigated the concentration-dependent effects of lincomycin on Streptomyces coelicolor. An et al. look at the impact salt stress has on translation in Medicago truncatula and Chevalier et al. present their ballistic model for determining kinetics rates during translation.
Phenomenological interpretations of the mechanism for the concentration-dependent positive effect of antibiotic lincomycin on Streptomyces coelicolor A3(2).
Applied and Environmental Microbiology, 2023.
Mukai, K., Shibayama, T., Imai, Y. and Hosaka, T.
The antibiotic, lincomycin, inhibits protein synthesis by binding to the peptidyl transferase loop region of 23S ribosomal RNA. However, it operates in a concentration-dependent manner. At concentrations below the minimum inhibitory concentration the production of the blue-pigmented antibiotic actinorhodin is stimulated.
In this study, the authors investigated this concentration-dependent effect of the ribosome-targeting lincomycin, employing the model actinomycete Streptomyces coelicolor A3(2), using ribosome profiling along with polysome profiling. The findings demonstrated that lincomycin, when present at a specific concentration which increases actinorhodin production in S. coelicolor A3(2), induced qualitative and quantitative alterations in ribosomes. It does so by utilising ribosome-related proteins and translation factors, potentially under the control of the WblC transcription factor, to produce stable and active ribosomes during the late growth phase. This positive ribosome alteration benefits actinorhodin biosynthesis. Furthermore, these lincomycin concentrations influenced the localization of 20S proteasome-related proteins, reducing proteasome activity.
This study holds significance in offering a phenomenological interpretation of the molecular mechanism underlying the concentration-dependent positive impact of lincomycin in S. coelicolor A3(2). It sheds new light on the potential role of antibiotics in fostering stability and activity in their target molecules, facilitated by various transcription associated factors that enhance their functionality. Delving deeper into this concept promises essential insights into antibiotics, exploring questions such as the reasons behind actinomycetes producing them and their broader role in nature.
Translational Landscape of Medicago truncatula Seedlings under Salt Stress
Journal of Agricultural and Food Chemistry, 2023
An, Y., Wang, Z., Liu, B., Cao, Y. and Chen, L.
Salt stress remains a prominent abiotic challenge faced by crops. Understanding the plant salt stress response is crucial for global food security and agricultural development. The Transcriptional response that plants have to salt stress has been extensively studied, however, its translational impact is far less researched.
In this study, the authors investigate translation regulation under salt stress in Medicago truncatula, a leguminous model plant closely related to Medicago sativa. Ribo-seq and RNA-seq analyses were conducted in M. truncatula seedlings grown under normal and salt stress conditions.
In response to salt stress, Ribo seq analysis revealed that 3944 genes exhibited inconsistent changes in transcriptional or translational levels, highlighting the independence of gene translation regulation in plant responses to environmental changes. Specifically, 2755 genes showed altered expression only at the translational level under salt stress, primarily associated with ribosome processes. Moreover, 3005 genes displayed consistent changes at both transcriptional and translational levels, with pathways like MAPK signaling and plant hormones implicated in salt stress response. This intricate gene regulation allows plants to flexibly adapt to external environmental changes, enhancing their resilience. The study also identified small ORFs, including uORFs in 5′UTRs, dORFs in 3′UTRs, and sORFs in lncRNAs, scattered throughout the M. truncatula genome.
These findings serve as a pertinent reference for future research on the plant’s response to salt stress.
Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model
PLoS Comput Biology 2023
Chevalier, C., Dorignac, J., Ibrahim, Y., Choquet, A., David, A., Ripoll, J., Rivals, E., Geniet, F., Walliser, NO., Palmeri, J., Parmeggiani, A. and Walter, JC.
The modeling of ribosome motion is conventionally done using 1D transport models like TASEP, enabling the derivation of kinetic rates (initiation and elongation) from Ribo-seq densities. However, existing methods do not provide access to mRNA degradation rates, and past experiments lack the necessary data for a self-consistent quantitative analysis. In response, this study introduces a novel experimental and modelling approach aimed at obtaining more accurate kinetic rates, including mRNA degradation.
The authors created a ballistic model of ribosome motion that can be applied to translatomics data where mRNAs are separated according to the number of ribosomes (k) attached to them (from 1 to 4 i.e., the mono-, di-, tri-, and tetra-somes fractions) via polysome profiling. By investigating the mean ribosome number (k), as well as polysome and k−some densities, the authors characterised the system based on three different mRNA degradation dependent regimes (low degradation (LD), intermediate degradation (ID) and high degradation (HD)).
This model was used on preliminary Ribo-seq data for a histone gene. From this, the authors report that the Ribo-seq data displays the same phenomenology predicted by the ballistic model in the ID regime: a decrease of the k−some Ribo-seq profiles at the end of the mRNA due to the degradation of mRNA in the late stages of translation. Thus, for the first time the effect of mRNA degradation on Ribo-seq data is shown.
This analysis reveals the crucial importance of mRNA lifetime in classifying genes. The main result is that although mRNA lifetime does not affect the polysome footprint, it does have a strong impact on the monosome one.