Sls1 and Mtf2 mediate the assembly of the Mrh5C complex required for activation of cox1 mRNA translation DOI Creative Commons
Yirong Wang, Ting Jin, Ying Huang

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(4), P. 107176 - 107176

Published: March 16, 2024

Mitochondrial translation depends on mRNA-specific activators. In Schizosaccharomyces pombe, DEAD-box protein Mrh5, pentatricopeptide repeat (PPR) Ppr4, Mtf2, and Sls1 form a stable complex (designated Mrh5C) required for of mitochondrial DNA (mtDNA)-encoded cox1 mRNA, the largest subunit cytochrome c oxidase complex. However, how Mrh5C is formed what role plays in mRNA have not been reported. To address these questions, we investigated individual subunits assembly function Mrh5C. Our results revealed that Mtf2 subcomplex serves as scaffold to bring Mrh5 Ppr4 together. binds small mitoribosome (mtSSU), but each could bind mtSSU independently. Importantly, association with mtSSU. Finally, importance signature Mrh5. We found Unexpectedly, this motif also interaction other subunits. Altogether, our suggest cooperate activating mRNA. activates by promoting recruitment

Language: Английский

The DEAD‐box RNA helicase ZmRH48 is required for the splicing of multiple mitochondrial introns, mitochondrial complex biosynthesis, and seed development in maize DOI Open Access
Yan‐Zhuo Yang, Shuo Ding, Xin‐Yuan Liu

et al.

Journal of Integrative Plant Biology, Journal Year: 2023, Volume and Issue: 65(11), P. 2456 - 2468

Published: Aug. 19, 2023

RNA helicases participate in nearly all aspects of metabolism by rearranging RNAs or RNA-protein complexes an adenosine triphosphate-dependent manner. Due to the large helicase families plants, precise roles many plant physiology and development remain be clarified. Here, we show that mutations maize (Zea mays) DEAD-box 48 (ZmRH48) impair splicing mitochondrial introns, complex biosynthesis, seed development. Loss ZmRH48 function severely arrested embryogenesis endosperm development, leading defective kernel formation. is targeted mitochondria, where its deficiency dramatically reduced efficiency five cis-introns (nad5 intron 1; nad7 introns 1, 2, 3; ccmFc 1) one trans-intron (nad2 2), lower levels I III. interacts with two unique pentatricopeptide repeat (PPR) proteins, PPR-SMR1 SPR2, which are required for over half introns. both proteins interact P-type PPR Zm-mCSF1 facilitate splicing. These results suggest likely a component critical biosynthesis

Language: Английский

Citations

11
DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs DOI Creative Commons
Hironori Saito, Yuma Handa, Mingming Chen

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 2, 2024

Small-molecule compounds that elicit mRNA-selective translation repression have attracted interest due to their potential for expansion of druggable space. However, only a limited number examples been reported date. Here, we show desmethyl desamino pateamine A (DMDA-PatA) represses in an manner by clamping eIF4A, DEAD-box RNA-binding protein, onto GNG motifs. By systematically comparing multiple eIF4A inhibitors ribosome profiling, found DMDA-PatA has unique mRNA selectivity repression. Unbiased Bind-n-Seq reveals DMDA-PatA-targeted exhibits preference motifs ATP-independent manner. This unusual RNA binding sterically hinders scanning 40S ribosomes. combination classical molecular dynamics simulations and quantum chemical calculations, the subsequent development inactive derivative positive charge tertiary amine on trienyl arm induces G selectivity. Moreover, identified DDX3, another is alternative target with same effects eIF4A. Our results provide example sequence-selective anchoring proteins inhibition protein synthesis small-molecule compounds. Here authors report DMDA-PatA, anti-tumor compound, functions as translational inhibitor. drug clamps DDX3 motif, providing steric hindrance

Language: Английский

Citations

4
Sequestration of SerRS through LLPS Impairs Localized Translation and Contributes to Antibiotic Persistence DOI Open Access
Ziyin Zhang,

D M Li,

Bo Zheng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Antibiotic-tolerant persisters contribute to the emergence of resistance, posing a significant challenge efficacy antibiotic therapies. Despite extensive research, mechanisms underlying persistence remain inadequately understood. By tracking evolution exponential-phase bacterial populations subjected intermittent high-dose ertapenem exposure, we characterized evolved strains in terms tolerance. Mutant strains, harboring mutations seryl-tRNA synthetase gene ( serS) , exhibited abrupt growth arrest upon serine depletion during exponential growth, resembling phenotype induced by hydroxamate (SHX). Under starvation, mutated SerRS protein was sequestrated into liquid-liquid phase separation (LLPS)-driven condensates, disrupting their composition and impairing localized translation. This event precipitated dormancy SerS T strain, triggering persistence. Our findings reveal an unrecognized role for aminoacyl-tRNA synthetases (aaRSs) modulating condensates provide insights molecular Graphic abstract Recruitment Disrupts Localized Translation DeaD-marked Condensates. Upon partitions LLPS-driven translation activity suggesting arising phase. These evolutionarily conserved orchestrate robust program enable stress responses instruct cell fate decisions populations.

Language: Английский

Citations

0
Structures and mRNP remodeling mechanism of the TREX-2 complex DOI
Yihu Xie, Bradley P. Clarke, Dongqi Xie

et al.

Structure, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Cellodextrin Metabolism and Phosphotransferase System‐Catalyzed Uptake in Enterococcus faecalis DOI Creative Commons
Victor Combret,

Isabelle Rincé,

Ronan Cochelin

et al.

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

Published: Feb. 13, 2025

Two PTS transporters involved in the uptake of cellobiose and short cellooligosaccharides were identified Enterococcus faecalis. Genes coding for different EII proteins are found a locus composed three operonic structures expressing two distinct EIIC (CelC1 CelC2), identical EIIB (CelB1 CelB2) unique EIIA (CelA1). The plays central role β-glucoside because it is required not only β-homodiholosides but also diheteroside N-acetylglucosamine-L-asparagine. Depending on their size, preferably transported either by CelC1 (di-saccharides) or CelC2 (4 glycosidic residues more), with tri-saccharides being taken up both transporters. Moreover, CelA1B2C2 require CelGHI to be functional, small proteins, function which remains unknown. CelA1B1C1 main exclusive transporter chitobiose. It transport other β-glucodisaccharides, such as laminaribiose sophorose. This can complemented highlighting existence network uptake. under control CelR, LevR-like transcription activator.

Language: Английский

Citations

0
Clinicopathological and prognostic significance of DDX41 mutation in myeloid neoplasms: a systematic review and meta-analysis DOI Creative Commons

Liying Miao,

Xin Wang, Minghui Yao

et al.

Annals of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract DDX41 is one of the most frequently altered genes in familial acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Mutation has been widely reported various types neoplasms. This systematic review and meta-analysis were conducted to assess clinical characteristics relationship between mutations OS neoplasm patients. We thoroughly searched PubMed, Cochrane Library, Embase, Web Science, MEDLINE, Google Scholar databases. Two reviewers separately reviewed extracted data. Twenty studies totaling 9,058 patients have integrated into meta-analysis. The extensive pooled analysis showed a significant association improved (HR 0.70, 95% CI 0.52–0.93, P = 0.01). Subgroup confirmed that mutation operated be reliable positive indicator when subdivided by different In terms clinicopathological value, significantly correlated with male sex. Age, AML prevalence, bone marrow, or white blood cell counts did not correlate any findings. top three genetic variants p.M1I, p.D140fs, p.R525H. Co-mutations commonly include following: additional sex combs-like 1 ( ASXL1 ), DNA methyltransferase 3 A DNMT3A tumor protein p53 TP53 ten-eleven translocation 2 TET2 ) serine/arginine-rich splicing factor SRSF2 ). Our results substantiate associated good provide more insight individuals

Language: Английский

Citations

0
Nucleolus activity-dependent recruitment and biomolecular condensation by pH sensing DOI Creative Commons
Fardin Aryan,

Diego Detrés,

Claire Luo

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(23), P. 4413 - 4423.e10

Published: Nov. 17, 2023

Language: Английский

Citations

9
Formation of the NLRP3 inflammasome inhibits stress granule assembly by multiple mechanisms DOI Creative Commons
Daisuke Yoshioka, Takanori Nakamura, Yuji Kubota

et al.

The Journal of Biochemistry, Journal Year: 2024, Volume and Issue: 175(6), P. 629 - 641

Published: Jan. 31, 2024

Abstract Proper regulation of cellular response to environmental stress is crucial for maintaining biological homeostasis and achieved by the balance between cell death processes, such as formation pyroptosis-inducing NLRP3 inflammasome, pro-survival granule (SG) assembly. However, functional interplay these two stress-responsive organelles remains elusive. Here, we identified DHX33, a viral RNA sensor SG component, SG-nucleating protein G3BP an inflammasome component. We also found that decrease in intracellular potassium (K+) concentration, key ‘common’ step activation, markedly inhibited Therefore, when macrophages are exposed stimuli with potential induce both SGs cytoplasmic poly(I:C) stimulation, they preferentially form but avoid assembly sequestering into inducing reduction K+ levels. Thus, under conditions, DHX33 primarily utilized inflammasome. Our data reveal crosstalk inflammasome-mediated pyroptosis SG-mediated survival pathways delineate molecular mechanism regulates cell-fate decisions anti-viral innate immunity stress.

Language: Английский

Citations

3
Me31B: a key repressor in germline regulation and beyond DOI Open Access
Ming Gao

Bioscience Reports, Journal Year: 2024, Volume and Issue: 44(5)

Published: April 12, 2024

Maternally Expressed at 31B (Me31B), an evolutionarily conserved ATP-dependent RNA helicase, plays important role in the development of germline across diverse animal species. Its cellular functionality has been posited as a translational repressor, participating various metabolism pathways to intricately regulate spatiotemporal expression RNAs. Despite its evident significance, precise and mechanistic underpinnings Me31B remain insufficiently understood. This article endeavors comprehensively review historic recent research on Me31B, distill major findings, discern generalizable patterns Me31B's functions different contexts, provide insights into fundamental mechanism action. The primary focus this centers elucidating Drosophila within germline, while concurrently delving pertinent orthologs other species systems.

Language: Английский

Citations

3
DDX19A promotes gastric cancer cell proliferation and migration by activating the PI3K/AKT pathway DOI Creative Commons
Yu Cheng, Yanjie Lu, Jing Xue

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Aug. 3, 2024

DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role gastric cancer remains unclear. The present study aimed to explore the and underlying mechanism of DDX19A development cancer.

Language: Английский

Citations

2