Spatiotemporal dynamics and selectivity of mRNA translation during mouse pre-implantation development DOI Creative Commons
Hao Ming, Rajan Iyyappan,

Kianoush Kakavand

et al.

Published: Oct. 28, 2024

Translational regulation is pivotal during preimplantation development. However, how mRNAs are selected for temporal and their dynamic utilization fate this period still unknown. Using a high-resolution ribosome profiling approach, we analyzed the transcriptome, as well monosome- polysome-bound RNAs of mouse oocytes embryos, defining an unprecedented extent spatiotemporal translational landscapes rapid developmental phase. We observed previously unknown mechanisms selectivity, i.e., stage-wise deferral loading monosome-bound to polysome active translation, continuous translation both monosome at same stage, priming monosomes after initial activation. showed that eukaryotic initiation factor Eif1ad3, which exclusively translated in 2-Cell embryo, required biogenesis post embryonic genome Our study thus provides genome-wide datasets analyses dynamics accompanying mammalian germ cell development reveals contribution novel pre-implantation

Language: Английский

Comparative proteomic landscapes elucidate human preimplantation development and failure DOI
Wencheng Zhu, Juan Meng, Yán Li

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

3
Degradation and translation of maternal mRNA for embryogenesis DOI Creative Commons
Guanghui Yang,

Qiliang Xin,

Jurrien Dean

et al.

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(3), P. 238 - 249

Published: Jan. 22, 2024

Language: Английский

Citations

13
eIF4E1b is a non-canonical eIF4E protecting maternal dormant mRNAs DOI Creative Commons
Laura Lorenzo‐Orts, Marcus Strobl,

Benjamin S. Steinmetz

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 25(1), P. 404 - 427

Published: Dec. 14, 2023

Abstract Maternal mRNAs are essential for protein synthesis during oogenesis and early embryogenesis. To adapt translation to specific needs development, maternal translationally repressed by shortening the polyA tails. While mRNA deadenylation is associated with decapping degradation in somatic cells, short tails stable. Here we report that germline-specific eIF4E paralog, eIF4E1b, zebrafish oogenesis. eIF4E1b localizes P-bodies embryos binds reported or no tails, including histone mRNAs. Loss of results reduced levels gonads, consistent a role storage. Using mouse human eIF4E1Bs (in vitro) vivo), show unlike canonical eIF4Es, does not interact eIF4G initiate translation. Instead, interacts translational repressor eIF4ENIF1, which required localization P-bodies. Our study an important regulating dormancy provides new insights into fundamental post-transcriptional regulatory principles governing vertebrate development.

Language: Английский

Citations

13
EIF4E1B interacts with HSPA1A and PPP2CA and is involved in mouse oocyte maturation and early embryonic development DOI

Zengyou Ma,

Yanyan Zhang,

Xueqi Tian

et al.

Theriogenology, Journal Year: 2025, Volume and Issue: unknown, P. 117398 - 117398

Published: March 1, 2025

Language: Английский

Citations

0
ZNHIT3 Regulates Translation to Ensure Cell Lineage Differentiation in Mouse Preimplantation Development DOI Creative Commons
Guanghui Yang,

Qiliang Xin,

Jurrien Dean

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Upon fertilization, the mouse zygotic genome is activated and maternal RNAs as well proteins are degraded. Early developmental programs built on encoded by genes that needed to guide early cell fate commitment. The box C/D snoRNA ribonucleoprotein (snoRNP) complex required for rRNA biogenesis, ribosome assembly pre-mRNA splicing essential protein translation. Zinc finger, HIT type 3 (encoded Znhit3) previously identified a component in of snoRNP complex. Using gene-edited mice, it identifies Znhit3 an embryonic gene whose ablation reduces translation prevents embryos development beyond morula stage. absence ZNHIT3 leads decreased abundance which causes defects ribosomes mRNA splicing. Microinjection cRNA partially rescues phenotype confirms during preimplantation development.

Language: Английский

Citations

0
The Reprogramming Power of the Oocyte DOI

Keith E. Latham

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Human Tissues Exhibit Diverse Composition of Translation Machinery DOI Open Access
Aleksandra S. Anisimova,

Natalia M. Kolyupanova,

Nadezhda E. Makarova

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8361 - 8361

Published: May 6, 2023

While protein synthesis is vital for the majority of cell types human body, diversely differentiated cells require specific translation regulation. This suggests specialization machinery across tissues and organs. Using transcriptomic data from GTEx, FANTOM, Gene Atlas, we systematically explored abundance transcripts encoding factors aminoacyl-tRNA synthetases (ARSases) in tissues. We revised a few known identified several novel translation-related genes exhibiting strict tissue-specific expression. The proteins they encode include eEF1A1, eEF1A2, PABPC1L, PABPC3, eIF1B, eIF4E1B, eIF4ENIF1, eIF5AL1. Furthermore, our analysis revealed pervasive relative components (e.g., PABP eRF3 paralogs, eIF2B eIF3 subunits, eIF5MPs, some ARSases), suggesting presumptive variance composition initiation, elongation, termination complexes. These conclusions were largely confirmed by proteomic data. Finally, paid attention to sexual dimorphism repertoire encoded sex chromosomes (eIF1A, eIF2γ, DDX3), testis brain as organs with most diverged expression translation-associated genes.

Language: Английский

Citations

7
Eif4enif1 haploinsufficiency disrupts oocyte mitochondrial dynamics and leads to subfertility DOI Creative Commons
Yuxi Ding,

Zequn He,

Yan-Wei Sha

et al.

Development, Journal Year: 2023, Volume and Issue: 150(23)

Published: Dec. 1, 2023

Infertility affects couples worldwide. Premature ovarian insufficiency (POI) refers to loss of function before 40 years age and is a contributing factor infertility. Several case studies have reported dominant-inherited POI symptoms in families with heterozygous EIF4ENIF1 (4E-T) mutations. However, the effects haploinsufficiency rarely been studied animal models reveal underlying molecular changes related Here, we demonstrate that Eif4enif1 causes mouse subfertility, impairs oocyte maturation partially arrests early embryonic development. Using dual-omic sequencing, observed significantly altered both transcriptome translatome oocytes, by which further revealed mitochondrial hyperfusion mitochondria-associated ribonucleoprotein domain distribution alteration Eif4enif1-deficient oocytes. This study provides new insights into mechanisms clinical fertility failure avenues pursue therapeutic targets address

Language: Английский

Citations

7
Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in the mouse uterus DOI Creative Commons

Qiliang Xin,

Iris Feng,

Guoyun Yu

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(5)

Published: Feb. 29, 2024

Early gestational loss occurs in approximately 20% of all clinically recognized human pregnancies and is an important cause morbidity. Either embryonic or maternal defects can loss, but a functioning receptive uterine endometrium crucial for embryo implantation. We report that the switch/sucrose nonfermentable (SWI/SNF) remodeling complex containing polybromo-1 (PBRM1) Brahma-related gene 1 (BRG1) essential implantation blastocyst on wall uterus mice. Although preimplantation development unaffected, conditional ablation Pbrm1 stromal cells disrupts progesterone pathways receptivity. Heart neural crest derivatives expressed 2 (Hand2) encodes basic helix-loop-helix (bHLH) transcription factor required identify enhancer Hand2 requires PBRM1 epigenetic histone modifications/coactivator recruitment looping with promoter. In Pbrm1cKO mice, perturbation chromatin assembly at promoter sites compromises transcription, adversely affects fibroblast growth signaling pathways, prevents normal stromal-epithelial crosstalk, The mutant female mice are infertile provide insight into potential causes early pregnancy humans.

Language: Английский

Citations

2
Oocyte‐specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse oocytes within the early‐growing follicles by mitochondrial fission defect‐reactive oxygen species‐DNA damage DOI Creative Commons
Weiyong Wang, Huiyu Liu, Shuang Liu

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

Abstract Background Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. Methods and results We generated eukaryotic factor 5 ( Eif5 ) conditional knockout mice aiming to investigate function of eIF5 during oocyte growth follicle development. Here, we demonstrated that deletion mouse primordial growing oocytes both resulted apoptosis within early‐growing follicles. Further studies revealed downregulated levels mitochondrial fission‐related proteins (p‐DRP1, FIS1, MFF MTFR) upregulated integrated stress response‐related (AARS1, SHMT2 SLC7A1) genes Atf4 , Ddit3 Fgf21 ). Consistent this, dysfunction characterized by elongated form, aggregated distribution beneath membrane, decreased adenosine triphosphate content mtDNA copy numbers, excessive accumulation reactive oxygen species (ROS) superoxide. Meanwhile, led a significant increase DNA damage response (γH2AX, p‐CHK2 p‐p53) proapoptotic (PUMA BAX), as well decrease anti‐apoptotic protein BCL‐xL. Conclusion These findings indicate follicles via fission defects, ROS damage. This study provides new insights into pathogenesis, genetic diagnosis potential therapeutic targets for POI. Key points leads arrest impairs proteins, followed dysfunction. Depletion causes pathway.

Language: Английский

Citations

2