March 16th, 2025
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,
- Mundodi et al. use ribosome profiling to investigate changes in translational and transcriptional gene expression in Candida albicans biofilm formation.
- Kibe et al. investigate HIV-1 gene regulation with ribosome profiling analysis.
- Sargen et al. use tRNA-seq to study that Salmonella uses a prophage-encoded defence system, called RemAIN to protect itself from lysis during prophage activation.
Ribosome profiling reveals differences in global translational vs transcriptional gene expression changes during early Candida albicans biofilm formation
Microbiology Spectrum, 2025
Mundodi, V., Choudhary, S., Smith, A.D. and Kadosh, D.
This study examines the complex gene regulation processes during the initial phases of biofilm development by Candida albicans. By employing ribosome profiling, the research highlights the variations in translational efficiency of genes compared to their transcriptional changes, underscoring the importance of post-transcriptional regulation in biofilm formation.
During the early stages of biofilm development (specifically the 6-hour mark post-adhesion), Candida albicans exhibits significant changes in gene expression. Ribosome profiling allowed for a detailed analysis, identifying specific genes and gene classes that showed altered translational efficiency. The findings reveal that while many genes are transcriptionally upregulated, including those involved in amino acid metabolism and cell wall synthesis, their translational efficiency can differ, providing insights into the layers of gene regulation at play.
Notably, the study discovered that genes related to essential biofilm functions like adhesion and matrix production are under complex translational control. This nuanced regulation suggests that interventions targeting translational mechanisms could be a novel approach to controlling biofilm-related pathogenicity.
Overall, the research demonstrates that ribosome profiling is a more accurate proxy for actual protein levels in the cell compared to transcriptional profiling, which can sometimes give an incomplete picture due to post-transcriptional modifications. This study lays the groundwork for potential therapeutic strategies that target the translational processes of biofilm formation, which could lead to the development of more effective antifungal treatments.
Learn more about EIRNA Bio’s ribosome profiling service here.
The translational landscape of HIV-1 infected cells reveals key gene regulatory principles
Nature Structural & Molecular Biology, 2025
Kibe, A., Buck, S., Gribling-Burrer, A-S., Gilmer, O., Bohn, P., Koch, T., Mireisz, C.N-M., Schlosser, A., Erhard, F., Smyth, R.P. and Caliskan, N.
This study explores the intricate mechanisms by which HIV-1 manages both viral and host gene expression to facilitate its lifecycle within host cells. Using ribosome profiling, disome sequencing, and RNA sequencing, the study provides a comprehensive view of how HIV-1 mRNAs are translated across different stages of infection. Interestingly, while HIV-1 mRNAs maintain high translational efficiency throughout the infection process, the translational efficiency of host genes, particularly those involved in cellular translation mechanisms, is significantly reduced.
The research highlights the discovery of upstream open reading frames in the HIV-1 5′-untranslated region and internal open reading frames within the Vif and Pol coding domains, which are critical for the virus’s ability to manipulate translation. Additionally, the study observes ribosomal collisions at specific sites upstream of the ribosome frameshift site in Gag-Pol, which are linked to a unique RNA structural fold. This structure appears pivotal for the virus as manipulating it with antisense oligonucleotides can decrease the frameshift efficiency, a potential target for antiviral therapies.
Overall, this study not only underscores the complexity of HIV-1 gene regulation but also provides crucial insights that could aid in the development of novel antiviral strategies by targeting specific elements within the virus’s translational machinery.
Learn more about EIRNA Bio’s ribosome profiling, disome-seq and RNA-seq services here.
A prophage competition element protects Salmonella from lysis
Cell Host & Microbiome, 2024
Sargen, M.R. and Helaine, S.
This paper investigates how Salmonella uses a prophage-encoded defence system, called RemAIN (ribonuclease effector module with ATPase, inhibitor, and nuclease), to protect itself from lysis during prophage activation. When Salmonella experiences DNA damage, such as within macrophages, prophages are induced, which can lead to bacterial cell lysis. The researchers found that RemAIN, encoded in the Gifsy-1 prophage, prevents the lytic cycles of co-residing prophages by cleaving tRNA at the anticodon loop, thereby blocking bacterial translation. This mechanism allows Salmonella persisters to survive within macrophages, influencing both bacterial persistence and host immune responses.
tRNA-seq is used in this study to investigate tRNA cleavage in Salmonella following prophage induction. Results showed that the RemA and RemN proteins work together to cleave tRNAs, with a strong preference for leucyl-, prolyl-, methionyl-(fMet), seryl-, and threonyl-tRNAs, primarily at the anticodon loop. This cleavage was observed both in a cell-free system and in Salmonella treated with mitomycin C (MMC), which crosslinks DNA. In strains lacking remN, tRNA cleavage was significantly reduced, confirming RemN as the primary nuclease responsible. This tRNA degradation disrupts bacterial translation, suggesting a regulatory mechanism that influences Salmonella‘s response to prophage activation.
The study provides a deep dive into the complex interactions between host and pathogen, including the sophisticated arms race between different prophage elements within a single bacterial host. This interplay is crucial for understanding how pathogens evade immune defences and could inform the development of new therapeutic strategies targeting these prophage systems.