bims-protra 2025-09-21 papers

Issue of 2025–09–21
three papers selected by
Marius d’Hervé, McGill University

bioRxiv. 2025 Sep 05. pii: 2025.01.13.632784. [Epub ahead of print]

Neuron type-specific mRNA translation programs provide a gateway for memory consolidation.

Mauricio M Oliveira, Olivia Mosto, Robert Carney, Wendy J Liu, Emmanuel Makinde, Catherine Leckie, Carson Schultz, Emily H Lu, Karen S A Ruiz, Thomas J Carew, Eric Klann.

Long-term memory consolidation is a dynamic process that requires a heterogeneous ensemble of neurons, each with a highly specialized molecular signature. Considerable effort has been devoted to identifying molecular changes that accompany the process of consolidation, but mostly hours or days after training, when memory consolidation is already complete. Studies have shown that protein synthesis is elevated during the early stages of consolidation, but how this increase impacts neuronal function remains unclear. We hypothesize that mRNAs translated during the early stages of consolidation could provide information on how diverse neurons involved in memory formation restructure their molecular signatures to support memory. Here, we generate a landscape of the translatome of three neuron types in the dorsal hippocampus during the first hour of contextual memory consolidation. Our results reveal that translation programs associated with consolidation are different among neurons, fueling the reconfiguration of specific biological processes. We further demonstrate the patterned translation of mRNAs in different neuron types during consolidation is explained by features hard-coded in the mRNA sequence, suggesting ubiquitous mechanisms controlling activity-induced neuronal translation. Altogether, our work uncovers previously unknown mechanisms controlling activity-induced translation in neurons and provides a large, readily available resource for scientists interested in the role of memory formation in health and disease.

DOI: https://doi.org/10.1101/2025.01.13.632784

Nucleic Acids Res. 2025 Sep 05. pii: gkaf902. [Epub ahead of print]53(17):

A simple, fast, and cost-efficient protocol for ultra-sensitive ribosome profiling.

Jiří Koubek, Katharina Jetzinger, Shiran Dror, Mikel Irastortza-Olaziregi, Dana Frank, Ilgin Kotan, Jaime Santos, Frank Tippmann, Pascal Lafrenz, Henrik Kaessmann, Orna Amster-Choder, Bernd Bukau, Günter Kramer.

Ribosome profiling has become an essential tool for studying messenger RNA (mRNA) translation in cells with codon-level resolution. However, its widespread application remains hindered by the labour-intensive workflow, low efficiency, and high costs associated with sequencing sample preparation. Here, we present a new cost-effective and ultra-sensitive library preparation method that significantly advances the applicability of ribosome profiling. By implementing bead-coupled enzymatic reactions and product purifications, our approach increases both yield and throughput while maintaining high reproducibility. Demonstrating the sensitivity of the protocol, we prepared libraries from as little as 12 fmol of RNA, which expands the feasibility of ribosome profiling from minimal input samples, such as those derived from small populations, stressed cells, or patient-derived specimens. Additionally, we validate the versatility of the protocol across multiple species and demonstrate its applicability for RNA-seq library preparation. Altogether, this protocol provides a highly accessible and efficient alternative to existing ribosome profiling workflows, facilitating research in previously challenging experimental contexts.

DOI: https://doi.org/10.1093/nar/gkaf902

PLoS Biol. 2025 Sep 18. 23(9): e3003403

Unconventional codon usage bias mediates mRNA translational dynamics in macrophages.

Shiqi Luo, Qiuyi Wang, Ao Chen, Liang Huang, Yaoqi Liu, Xin Zong, Yuanhui Mao.

Macrophages require rapid and tightly controlled regulatory mechanisms to respond to environmental disruptions. While transcriptional regulation has been well characterized, the mechanisms underlying translational control in macrophages remain poorly understood. Here, we investigated the dynamics of mRNA translation in mouse macrophages during acute, intermediate, and prolonged LPS exposure. Our results reveal clear phase-specific translational regulation during macrophage polarization, which initially increases the synthesis of inflammatory mediators and cytokines, while simultaneously suppressing the expression of cell cycle-related genes. Mechanistically, we observed pervasive upstream translation in the 5' UTRs of cell cycle-related mRNAs, which contributes to cell cycle arrest during the early phase of inflammatory response. Notably, we identified a unique codon preference toward A/U in the third position of codons in macrophages, which contrasts with the G/C preference commonly observed in other tissues. AU codon preference increases the stability and translation efficiency of cell cycle-related mRNAs, promoting cell cycle restoration after extended LPS exposure. These findings reveal that uORF translation and codon usage bias are critical components of translational regulation during macrophage polarization, highlighting a potential therapeutic intervention for modulating immune activation via macrophage-specific codon optimization.

DOI: https://doi.org/10.1371/journal.pbio.3003403