PRMT5 mediates FoxO1 methylation and subcellular localization to regulate lipophagy in myogenic progenitors

Kim, Kun Ho; Oprescu, Stephanie N.; Snyder, Madigan M.; Kim, Aran; Jia, Zhihao; Yue, Feng; Kuang, Shihuan

doi:10.1016/j.celrep.2023.113329

Cited by 4 publications

(2 citation statements)

References 86 publications

(113 reference statements)

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“…Autophagy (“self-feeding”) is a tightly regulated process that delivers senescent intracellular components to lysosomes for degradation to maintain intracellular homeostasis [ 20 , 21 ]. Recent studies have shown that autophagy regulation is closely related to human health [ 22 ]. After SCI, an inhibitory microenvironment is formed in the lesion area, and adult neurons exhibit poor intrinsic growth potential [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop

Zhang,

Xiao,

et al. 2024

J Orthop Surg Res

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Spinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop

Zhang,

Xiao,

et al. 2024

J Orthop Surg Res

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“…KDM5B can also be involved in the immune escape mechanism of melanoma in combination with HMT SETDB1 [ 142 ]. PRMT5 is elevated in various hematologic malignancies and solid cancers and is responsible for maintaining muscle development and regeneration under normal physiology [ 143 – 146 ]. However, PRMT5 has more than just a promoting effect in cancer, and it has been confirmed that PRMT5 has a tumor-suppressive effect in clear cell renal cell carcinoma [ 147 ].…”

Section: Types Of Chromatin Modifiersmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

Cao,

Wang,

Liu

et al. 2024

Preprint

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Various posttranslational modifications (PTMs) have been implicated in endometrial stromal cell (EnSC) differentiation, but the potential role of PTM crosstalk has not been identified. Here, we report that protein arginine methyltransferase 5 (PRMT5) is indispensable for human endometrial decidualization, functioning as a key regulator of decidualization defect in recurrent implantation failure (RIF) patients. Uterine-selective deletion ofPrmt5led to defective embryo implantation in mice due to impaired EnSC decidualization. Mechanistically, we find that PRMT5 catalyzes symmetric dimethylation of orphan nuclear receptor Nur77 at arginine 346, which in turn promotes Nur77 nuclear localization and increases its transcriptional activity in EnSC. Moreover, we demonstrate that PRMT5-mediated Nur77 methylation antagonizes AKT-induced phosphorylation of Nur77 at serine 351 in the transition from proliferation to differentiation of EnSC and disruption of the balance between methylation and phosphorylation of Nur77 is essentially involved in the endometrium of RIF patients. Furthermore, by modulating the methylation-phosphorylation of Nur77 and its transcriptional activity, we rescued impaired decidualization in RIF, further highlighting the critical role of the PRMT5/AKT/Nur77 complex in uterine receptivity to embryo implantation.

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PRMT5 mediates FoxO1 methylation and subcellular localization to regulate lipophagy in myogenic progenitors

Cited by 4 publications

References 86 publications

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop

Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

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