bims-spribo 2026-08-23 papers

Issue of 2026–08–23
two papers selected by
Maxim Bouvet, L'Università di Torino

bioRxiv. 2026 Jul 30. pii: 2026.07.29.740946. [Epub ahead of print]

Anticodon nucleotide modifications affect translational tuning by the ribosomal CAR surface.

Mitsu Raval, Yancheng Zhou, Mia Wichman, Miki Lynch, Daniel Krizanc, Kelly M Thayer, Michael P Weir.

Nucleotide modifications of the tRNA anticodon can affect protein translation fidelity and speed. Chemical modifications of the anticodon nucleotide 34 are regulated under cellular stress and associated with several translational defects and pathologies. Here, we investigate how these modifications influence A-site codon recognition interactions and their coupling to the CAR site that lies adjacent to nucleotide 34 in the ribosome. The conserved three-residue CAR interface hydrogen bonds in a sequence-dependent manner to the mRNA +1 codon 3'-adjacent to the A-site codon and is implicated in tuning translational speed. The C of CAR is pi-stacked with the nucleotide 34 of the A site tRNA anticodon. The A site and the CAR site influence each other's hydrogen bonding and stacking interactions, and these codon-adjacency effects potentially provide a layer of regulation affecting translational fidelity and kinetics. Through molecular dynamics simulations of a subsystem of a translocating ribosome IRES-model, we observed that nucleotide 34 modifications affect the hydrogen bonding and stacking interactions at the A site and CAR site as well as CAR's influence on the A site interactions. Integrating these results with gene sequence and ribosome profiling analyses, we propose that nucleotide 34 modifications help modulate CAR's sequence-dependent tuning of translation in response to cellular stress.
Graphical abstract:

DOI: https://doi.org/10.64898/2026.07.29.740946

Circ Res. 2026 Aug 21.

Single-Molecule Imaging Reveals ERK-Dependent Spatial Translation in Cardiomyocytes.

Itai Erlich, Guy Douvdevany, Rami Haddad, Benjamin L Prosser, Izhak Kehat.

BACKGROUND: Translational control of gene expression is crucial in cardiomyocytes, particularly in response to hypertrophic stimuli. The ERK (extracellular signal-regulated kinase) pathway plays a key role in inducing cardiac hypertrophy and regulating specific protein translation. However, it remains unclear how this specificity is achieved, and the spatiotemporal regulation of protein translation is not fully understood.
METHODS: We used SINAP (single-molecule imaging of nascent peptide) reporters to visualize and analyze the translation dynamics in single adult rat ventricular cardiomyocytes and tracked active translation sites at high spatiotemporal resolution. We also examined the effects of adrenergic stimulation and the role of the ERK pathway in translation localization.
RESULTS: Our findings revealed that translation sites are primarily localized near Z-lines in cardiomyocytes, with some sites being highly dynamic and moving during translation. The 3' untranslated regions did not significantly change the localization of translation. Many translation sites colocalized with microtubules, and their movement predominantly occurred along microtubular tracks. Adrenergic stimulation led to a transient shift in translation activity toward the perinuclear region, peaking at 12 hours and requiring ERK pathway activity for this localization change. This shift is part of the hypertrophic response and is required for early translation of genes such as Nppa.
CONCLUSIONS: Our high-resolution single-cell study demonstrates that protein translation in cardiomyocytes is dynamic and responsive to hypertrophic stimuli in an ERK-dependent manner. The localized translation mechanism allows cardiomyocytes to rapidly adapt to changing environments by preferentially translating mRNAs in the perinuclear region. These findings provide new insights into the spatial regulation of translation in cardiomyocytes and its role in cardiac hypertrophy.

Keywords: adult; myocytes, cardiac; neurons; phosphorylation; serotonin

DOI: https://doi.org/10.1161/CIRCRESAHA.126.329033