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Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

ABSTRACT: Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized. Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. Deletion of Tssa led to male sterility and absence of sperm formation. The spermiogenesis arrested at the round spermatid stage and numerous spermiogenic mRNAs were down-regulated in Tssa-/- mice. Deletion of Tssa disrupted the localization of Miwi to chromatoid body, a specialized assembly of cytoplasmic messenger ribonucleoproteins (mRNPs) foci present in germ cells. We found that Tssa interacted with Miwi in repressed mRNPs and stabilized Miwi-interacting spermiogenesis-essential mRNAs. Our findings indicate that Tssa is indispensable in male fertility and has critical roles in post-transcriptional regulations by interacting with Miwi during spermiogenesis.

SUBMITTER: Chen Y

PROVIDER: S-EPMC10111675 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

Chen Yu Y Zhang Xiangzheng X Jiang Jiayin J Luo Mengjiao M Tu Haixia H Xu Chen C Tan Huanhuan H Zhou Xin X Chen Hong H Han Xudong X Yue Qiuling Q Guo Yueshuai Y Zheng Ke K Qi Yaling Y Situ Chenghao C Cui Yiqiang Y Guo Xuejiang X

BMC biology 20230417 1

<h4>Background</h4>Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized.<h4>Results</h4>Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. De ...[more]

PMID: 37069605

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Project description:In plants, macroautophagy/autophagy has mainly been associated with stress-related processes but how it impacts normal physiological and developmental processes remains largely unexplored. Pollen germination is the critical first step toward fertilization in flowering plants. It is metabolically demanding and relies on high levels of cytoplasmic reorganization activities to support a dramatic morphological transformation that underlies the development of a pollen tube as the conduit to deliver sperm for fertilization. The role of autophagy in this process remains unclear. Here we provide evidence that pollen germination is accompanied by elevated autophagic activity and successful pollen tube emergence depends on autophagy-mediated cytoplasmic deletion. Genetic and cytological experiments demonstrate that inhibition of autophagy prevents pollen germination while induces the persistence of a layer of undegraded cytoplasm at the germination aperture. Together, these results unveil a novel compartmentalized autophagy. Furthermore, high-throughput comparative lipidomic analyses show that suppressed autophagy-induced inhibition of pollen germination is accompanied by altered profiles of stored and signaling lipids. Proteomic analyses reveal that autophagy likely exert its role in pollen germination via downstream mitochondria-related pathways. These findings reveal a critical role for autophagy in initiating pollen germination and provide evidences for compartmental cytoplasmic deletion being crucial for male fertility. Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy-related gene; Cer: ceramide; CL: cardiolipin; Con A: concanamycin A; DAG: diradylglycerol; GO: gene ontology; HAG: hour after germination; LC-MS: liquid chromatography-mass spectrometry; MAG: min after germination; MDC: monodansylcadaverine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; PLD: phospholipase D; PtdIns3K: phosphatidylinositol 3-kinase; RT-qPCR: quantitative real-time reverse transcription PCR; TAG: triradylglycerol; TEM: transmission electron microscopy; TMT: tandem mass tagging.

Project description:BackgroundRecent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined.MethodsCircular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells.ResultsCirc-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U (hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases (GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients.ConclusionsThese findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

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Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

Publications

Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

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