Conserved Function of Drg GTPases in Promoting Protein Synthesis in Stalled Ribosomes DOI Creative Commons
Christopher Hawk, Hong Jin

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 21, 2024

Abstract Maintaining proper protein homeostasis is essential for cell physiology. The ribosome and GTPases, which are two of the most ancient critical cellular molecules, central players in synthesis its regulation. Here we report discovery a new general translation factor that targets stalled ribosomes promotes an evolutionarily conserved manner. We show bacterial Obg GTPases distant homologs eukaryotic archaeal Drg proteins serve roles promoting efficient ribosomes. Through vivo characterization, including cross-species complementation cells where induced to stall by addition either antibiotic anisomycin or exogenous mRNA harboring long poly(A) sequence, demonstrate function alleviate ribosomal stalling during translation. Our data rescues both Saccharomyces cerevisiae human lacking endogenous Drgs, as does supplementation respective from yeast cells. Furthermore, presence ObgE GTP stimulates peptidyl transfer, key catalytic ribosome, suggesting possible molecular mechanism this GTPase enhance This shows directly affords three domains life form

Language: Английский

Cytoplasmic mRNA decay and quality control machineries in eukaryotes DOI
Megan E. Dowdle, Jens Lykke‐Andersen

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

1
Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision DOI Creative Commons
Annika Bestehorn,

Julius von Wirén,

Christina Zeiler

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
lncRNAs: the unexpected link between protein synthesis and cancer adaptation DOI Creative Commons
Mila Gugnoni, Manoj Kumar Kashyap, Kishore K. Wary

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 31, 2025

Cancer progression relies on the ability of cells to adapt challenging environments overcoming stresses and growth constraints. Such adaptation is a multifactorial process that depends rapid reorganization many basic cellular mechanisms. Protein synthesis often dysregulated in cancer, translational reprogramming emerging as driving force cancer adaptive plasticity. Long non-coding RNAs (lncRNAs) represent main product genome transcription. They outnumber mRNAs by an order magnitude their expression regulated extremely specific manner depending context, space time. This heterogeneity functional allows lncRNAs act context-specific, fine-tuning controllers gene expression. Multiple recent evidence underlines how, besides consolidated role transcription, are major players translation control. Their capacity establish multiple highly dynamic interactions with proteins other transcripts makes these molecules able play central across all phases protein synthesis. Even if through myriad different mechanisms, action dual. On one hand, modulating overall speed, participate metabolic under stress conditions. prioritizing they help maintain high levels essential oncogenes. In this review, we aim discuss most relevant regarding involvement regulation how function may affect plasticity resistance stress. We also expect provide first collective perspectives way modulate beyond

Language: Английский

Citations

0
The ribosome as a platform to coordinate mRNA decay DOI Creative Commons
Martin Müller, Thomas Becker, Timo Denk

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: Jan. 30, 2025

Messenger RNA (mRNA) homeostasis is a critical aspect of cellular function, involving the dynamic interplay between transcription and decay processes. Recent advances have revealed that ribosome plays central role in coordinating mRNA decay, challenging traditional view free primary substrate for degradation. This review examines mechanisms whereby ribosomes facilitate both licensing execution decay. involves factors such as Ccr4-Not complex, small MutS-related domain endonucleases, various quality control pathways. We discuss how translational fidelity, well presence nonoptimal codons collisions, can trigger pathways nonstop no-go Furthermore, we highlight direct association canonical exonucleases, Xrn1 Ski-exosome system, with ribosome, underscoring ribosome's multifaceted platform regulatory processes governing stability. By integrating recent findings, this offers comprehensive overview structural basis not only translation but also serve hubs coordination.

Language: Английский

Citations

0
Less is more: slow-codon windows enhance eGFP mRNA resilience against RNA interference DOI Creative Commons
Judith Müller,

Gerlinde Schwake,

Anita Reiser

et al.

Journal of The Royal Society Interface, Journal Year: 2025, Volume and Issue: 22(224)

Published: March 1, 2025

Extensive efforts have been devoted to enhancing the translation efficiency of mRNA delivered mammalian cells via codon optimization. However, impact choice on stability remains underexplored. In this study, we investigated influence usage degradation kinetics in cultured human cell lines using live-cell imaging single-cell arrays. By measuring lifetimes at level for synthetic constructs, confirmed that mRNAs containing slowly translated windows shorter lifetimes. Unexpectedly, these did not exhibit decreased presence small interfering RNA (siRNA) compared with unmutated sequence, suggesting an interference different concurrent mechanisms. We employed stochastic simulations predict ribosome density along open reading frame, revealing densities correlated a cell-type- and codon-position-specific manner. summary, our results suggest effect its lifetime is context-dependent respect type, position interference.

Language: Английский

Citations

0
Sustainable regeneration of 20 aminoacyl-tRNA synthetases in a reconstituted system toward self-synthesizing artificial systems DOI Creative Commons
Katsumi Hagino,

Keiko Masuda,

Yoshihiro Shimizu

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(14)

Published: April 2, 2025

In vitro construction of self-reproducible artificial systems is a major challenge in bottom-up synthetic biology. Here, we developed reconstituted system capable sustainably regenerating all 20 aminoacyl-transfer RNA synthetases (AARS), which are components the translation system. To achieve this, needed five types improvements: (i) optimization AARS sequences for efficient translation, (ii) composition to enhance (iii) employment another bacterial AlaRS and SerRS improve each aminoacylation activity, (iv) diminishing translational inhibition caused by certain codon EF-P addition, (v) balancing DNA concentrations match requirement. After these improvements, succeeded sustainable regeneration up cycles 2.5-fold serial dilutions. These methodologies results provide substantial advancement toward realization systems.

Language: Английский

Citations

0
Are Bacterial Processes Dependent on Global Ribosome Pausing Affected by tRNA Modification Defects? DOI
Valérie de Crécy‐Lagard,

Zeynep Barahoglu,

Yifeng Yuan

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169107 - 169107

Published: April 1, 2025

Language: Английский

Citations

0
UFMylation orchestrates spatiotemporal coordination of RQC at the ER DOI Creative Commons
Ivan Penchev, Samantha C. Gumbin, Francesco Scavone

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(18)

Published: May 2, 2025

Degradation of arrest peptides from endoplasmic reticulum (ER) translocon-bound 60 S ribosomal subunits via the ribosome-associated quality control (ER-RQC) pathway requires covalent modification RPL26/uL24 on with UFM1. However, underlying mechanism that coordinates UFMylation and RQC pathways remains elusive. Structural analysis ER-RQC intermediates revealed concomitant binding direct interaction machineries . In presence an arrested peptidyl–transfer RNA, factor NEMF UFM1 E3 ligase (E3 ) form a UFL1 subunit , adopts conformation distinct previously observed for posttermination While this occurs LTN1 recruitment peptide degradation require UFMylation-dependent dissociation translocon. These data reveal by which cycle orchestrates ER-RQC.

Language: Английский

Citations

0
Comprehensive characterization of fatty acid oxidation in triple-negative breast cancer: Focus on biological roles and drug modulation DOI

Yunduo Liu,

Yanxia Zhang, Qin Xiang

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177343 - 177343

Published: Feb. 1, 2025

Language: Английский

Citations

0
RIOK3 mediates the degradation of 40S ribosomes DOI Creative Commons
Zixuan Huang,

Frances F. Diehl,

Mengjiao Wang

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Cells tightly regulate ribosome homeostasis to adapt changing environments. Ribosomes are degraded during stress, but the mechanisms responsible remain unclear. Here, we show that starvation induces selective depletion of 40S ribosomes following their ubiquitylation by E3 ligase RNF10. The atypical kinase RIOK3 specifically recognizes these ubiquitylated through a unique ubiquitin-interacting motif, visualized cryoelectron microscopy (cryo-EM). binding and ubiquitin recognition essential for degradation starvation. progressive decay 18S rRNA beginning at 3' end, as revealed cryo-EM structures intermediates. Together, data define pathway mechanism stress-induced ribosomes, directly connecting regulation homeostasis.

Language: Английский

Citations

0