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Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE221643 | GEO | 2024/10/08

REPOSITORIES: GEO

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Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (scRNA-Seq)

Project description:Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

2024-10-08 | GSE221642 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (RNA-Seq)

2024-10-08 | GSE221641 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Ribo-Seq)

2024-10-08 | GSE221640 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Polysome-Seq)

2024-10-08 | GSE221639 | GEO

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

| PRJNA915107 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Polysome-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Polysome-Seq)

| PRJNA915109 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Ribo-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (Ribo-Seq)

| PRJNA915110 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (scRNA-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (scRNA-Seq)

| PRJNA915112 | ENA

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (RNA-Seq)

Project description:Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control (RNA-Seq)

| PRJNA915111 | ENA

Relevance of the Axis Spermidine/eIF5A for Plant Growth and Development.

Project description:One key role of the essential polyamine spermidine in eukaryotes is to provide the 4-aminobutyl moiety group destined to the post-translational modification of a lysine in the highly conserved translation factor eIF5A. This modification is catalyzed by two sequential enzymatic steps leading to the activation of eIF5A by the conversion of one conserved lysine to the unusual amino acid hypusine. The active translation factor facilitates the sequence-specific translation of polyproline sequences that otherwise cause ribosome stalling. In spite of the well-characterized involvement of active eIF5A in the translation of proline repeat-rich proteins, its biological role has been recently elucidated only in mammals, and it is poorly described at the functional level in plants. Here we describe the alterations in plant growth and development caused by RNAi-mediated conditional genetic inactivation of the hypusination pathway in Arabidopsis thaliana by knocking-down the enzyme deoxyhypusine synthase. We have uncovered that spermidine-mediated activation of eIF5A by hypusination is involved in several aspects of plant biology such as the control of flowering time, the aerial and root architecture, and root hair growth. In addition this pathway is required for adaptation to challenging growth conditions such as high salt and high glucose medium and to elevated concentrations of the plant hormone ABA. We have also performed a bioinformatic analysis of polyproline-rich containing proteins as putative eIF5A targets to uncover their organization in clusters of protein networks to find molecular culprits for the disclosed phenotypes. This study represents a first attempt to provide a holistic view of the biological relevance of the spermidine-dependent hypusination pathway for plant growth and development.

| S-EPMC4773603 | biostudies-literature

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