Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE235017 | GEO | 2024/03/13
REPOSITORIES: GEO
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Project description:Male sterility is an important trait in hybrid crop breeding. Thermo-sensitive genic male sterility (TGMS) lines, which are male-sterile at restrictive (high) temperatures but convert to male-fertile at permissive (low) temperatures, have been widely utilized in two-line hybrid rice breeding3. However, the molecular mechanism underlying TGMS remains unclear. Here we show that the rice (Oryza sativa L.) thermo-sensitive genic male sterile gene 5 (tms5) locus, which in 2010 was present in cultivars occupying more than 70% (2.4 million hectares) of two-line hybrid rice-growing land in China, confers the TGMS trait through a loss-of-function mutation of RNase ZS1, resulting in failure to mediate mRNA decay of three temperature-responsive ubiquitin fusion ribosomal protein L40 genes (UbL40). TMS5 encodes an evolutionarily conserved endonuclease, RNase ZS1. RNase ZS1 can process tRNAs in vitro, but does not do so in vivo due to its localization in the cytoplasm. Defective RNase ZS1 in tms5 plants leads to over-accumulation of UbL401, UbL402 and UbL404 mRNAs at restrictive but not permissive temperatures. Furthermore, over-expression of UbL401 and UbL404 in wild-type plants causes male sterility, while knockdown of UbL401 and UbL404 in tms5 partially restores its fertility. Our results uncover a novel mechanism of RNase ZS1-mediated UbL40 mRNA decay which controls TGMS in rice and has potential applications in hybrid breeding not only of rice but also of other crops. Examination of differences in mRNA accumulation between 93-11, NIL5 and NIL8.
2014-09-11 | E-GEOD-42314 | biostudies-arrayexpress
Project description:We identified SMYD5 (SET and MYND Domain-Containing Protein 5) physiologically methylates core ribosomal protein L40 at lysine 22 (rpL40K22me3).In mouse GAC model, we observed rpL40K22me3 stoichiometry is saturating in both normal and GAC tissue.
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Project description:Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 at lysine 22 (rpL40K22me3) by the lysine methyltransferase (KMT) SMYD5 regulates mRNA translation output to promote gastric adenocarcinoma (GAC) malignant progression with lethal peritoneal ascites. A biochemical-proteomic strategy identifies the mono-ubiquitin fusion protein partner rpL40 as the principal physiologic substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprograms protein synthesis to attenuate oncogenic gene expression signatures. SMYD5 and rpL40K22me3 are upregulated in GAC patient samples and negatively correlate with clinical outcomes. SMYD5 ablation in vivo in familial and sporadic mouse models of malignant GAC blocks metastatic disease including peritoneal carcinomatosis (PC). Suppressing SMYD5 methylation of rpL40 inhibits human cancer cell and patient-derived GAC xenograft growth and renders them hypersensitive to PI3K/mTOR inhibitors. Finally, combining SMYD5 depletion with PI3K/mTOR inhibition and CAR-T administration cures an otherwise lethal in vivo mouse model of aggressive GAC-derived PC. Together, our work uncovers a ribosome-based epigenetic mechanism that facilitates evolution of malignant GAC and nominates SMYD5 targeting as part of a potential cornerstone combination therapy to treat a deadly cancer.
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Project description:We identified SMYD5 (SET and MYND Domain-Containing Protein 5) physiologically methylates core ribosomal protein L40 at lysine 22 (rpL40K22me3). rpL40K22me3 depletion upon SMYD5 knockdown in GAC KKLS cells was observed by targeted-mass spectrometry of immunoprecipitated rpL40.
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Project description:Male sterility is an important trait in hybrid crop breeding. Thermo-sensitive genic male sterility (TGMS) lines, which are male-sterile at restrictive (high) temperatures but convert to male-fertile at permissive (low) temperatures, have been widely utilized in two-line hybrid rice breeding. However, the molecular mechanism underlying TGMS remains unclear. Here we show that the rice (Oryza sativa L.) thermo-sensitive genic male sterile gene 5 (tms5) locus, which in 2010 was present in cultivars occupying more than 71% (2.3 million hectares) of two-line hybrid rice-growing land in China, confers the TGMS trait through a loss-of-function mutation of RNase ZS1, resulting in failure to mediate mRNA decay of three temperature-responsive ubiquitin fusion ribosomal protein L40 genes (UbL40) genes. RNase ZS1, a member of the evolutionarily conserved endonuclease, processed tRNAs in vitro, but does not do so in vivo due to its localization in the cytoplasm. Defective RNase ZS1 in tms5 plants leads to over-accumulation of UbL401, UbL402 and UbL404 mRNAs at restrictive but not permissive temperatures. Over-expression of UbL401 and UbL404 in wild-type plants caused male sterility, whereas knockdown of UbL401 and UbL404 in tms5 plants partially restored the male fertility at restrictive temperatures. Our results uncover a novel mechanism of RNase ZS1-mediated UbL40 mRNA decay which controls TGMS in rice and has potential applications not only of rice but also of other crops. To address whether RNase ZS1 involves in mRNA metabolism, whole-genome microarray was performed using RNA from young panicles of wild type (AnN and ZH11) and tms5 (AnS-1 and Os02g12290iL1) plants grown at permissive and restrictive temperatures.
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Project description:Male sterility is an important trait in hybrid crop breeding. Thermo-sensitive genic male sterility (TGMS) lines, which are male-sterile at restrictive (high) temperatures but convert to male-fertile at permissive (low) temperatures, have been widely utilized in two-line hybrid rice breeding. However, the molecular mechanism underlying TGMS remains unclear. Here we show that the rice (Oryza sativa L.) thermo-sensitive genic male sterile gene 5 (tms5) locus, which in 2010 was present in cultivars occupying more than 80% (2.6 million hectares) of two-line hybrid rice-growing land in China, confers the TGMS trait through a loss-of-function mutation of RNase ZS1, resulting in failure to mediate mRNA decay of three temperature-responsive ubiquitin fusion ribosomal protein L40 genes (UbL40) genes. RNase ZS1, a member of the evolutionarily conserved endonuclease, processed tRNAs in vitro, but does not do so in vivo due to its localization in the cytoplasm. Defective RNase ZS1 in tms5 plants leads to over-accumulation of UbL401, UbL402 and UbL404 mRNAs at restrictive but not permissive temperatures. Over-expression of UbL401 and UbL404 in wild-type plants caused male sterility, whereas knockdown of UbL401 and UbL404 in tms5 plants partially restored the male fertility at restrictive temperatures. Our results uncover a novel mechanism of RNase ZS1-mediated UbL40 mRNA decay which controls TGMS in rice and has potential applications not only of rice but also of other crops. To address whether RNase ZS1 involves in mRNA metabolism, degradome sequencing was performed using RNA from young panicles of wild type (ZH11) and tms5 (Os02g12290iL1) plants grown at restrictive temperatures.
2016-08-01 | E-GEOD-42467 | biostudies-arrayexpress
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Project description:Male sterility is an important trait in hybrid crop breeding. Thermo-sensitive genic male sterility (TGMS) lines, which are male-sterile at restrictive (high) temperatures but convert to male-fertile at permissive (low) temperatures, have been widely utilized in two-line hybrid rice breeding. However, the molecular mechanism underlying TGMS remains unclear. Here we show that the rice (Oryza sativa L.) thermo-sensitive genic male sterile gene 5 (tms5) locus, which in 2010 was present in cultivars occupying more than 80% (2.6 million hectares) of two-line hybrid rice-growing land in China, confers the TGMS trait through a loss-of-function mutation of RNase ZS1, resulting in failure to mediate mRNA decay of three temperature-responsive ubiquitin fusion ribosomal protein L40 genes (UbL40) genes. RNase ZS1, a member of the evolutionarily conserved endonuclease, processed tRNAs in vitro, but does not do so in vivo due to its localization in the cytoplasm. Defective RNase ZS1 in tms5 plants leads to over-accumulation of UbL401, UbL402 and UbL404 mRNAs at restrictive but not permissive temperatures. Over-expression of UbL401 and UbL404 in wild-type plants caused male sterility, whereas knockdown of UbL401 and UbL404 in tms5 plants partially restored the male fertility at restrictive temperatures. Our results uncover a novel mechanism of RNase ZS1-mediated UbL40 mRNA decay which controls TGMS in rice and has potential applications not only of rice but also of other crops.
2016-08-01 | GSE42467 | GEO
Project description:Male sterility is an important trait in hybrid crop breeding. Thermo-sensitive genic male sterility (TGMS) lines, which are male-sterile at restrictive (high) temperatures but convert to male-fertile at permissive (low) temperatures, have been widely utilized in two-line hybrid rice breeding3. However, the molecular mechanism underlying TGMS remains unclear. Here we show that the rice (Oryza sativa L.) thermo-sensitive genic male sterile gene 5 (tms5) locus, which in 2010 was present in cultivars occupying more than 70% (2.4 million hectares) of two-line hybrid rice-growing land in China, confers the TGMS trait through a loss-of-function mutation of RNase ZS1, resulting in failure to mediate mRNA decay of three temperature-responsive ubiquitin fusion ribosomal protein L40 genes (UbL40). TMS5 encodes an evolutionarily conserved endonuclease, RNase ZS1. RNase ZS1 can process tRNAs in vitro, but does not do so in vivo due to its localization in the cytoplasm. Defective RNase ZS1 in tms5 plants leads to over-accumulation of UbL401, UbL402 and UbL404 mRNAs at restrictive but not permissive temperatures. Furthermore, over-expression of UbL401 and UbL404 in wild-type plants causes male sterility, while knockdown of UbL401 and UbL404 in tms5 partially restores its fertility. Our results uncover a novel mechanism of RNase ZS1-mediated UbL40 mRNA decay which controls TGMS in rice and has potential applications in hybrid breeding not only of rice but also of other crops.
2014-09-11 | GSE42314 | GEO
Project description:Male sterility is an important trait in hybrid crop breeding. Thermo-sensitive genic male sterility (TGMS) lines, which are male-sterile at restrictive (high) temperatures but convert to male-fertile at permissive (low) temperatures, have been widely utilized in two-line hybrid rice breeding. However, the molecular mechanism underlying TGMS remains unclear. Here we show that the rice (Oryza sativa L.) thermo-sensitive genic male sterile gene 5 (tms5) locus, which in 2010 was present in cultivars occupying more than 71% (2.3 million hectares) of two-line hybrid rice-growing land in China, confers the TGMS trait through a loss-of-function mutation of RNase ZS1, resulting in failure to mediate mRNA decay of three temperature-responsive ubiquitin fusion ribosomal protein L40 genes (UbL40) genes. RNase ZS1, a member of the evolutionarily conserved endonuclease, processed tRNAs in vitro, but does not do so in vivo due to its localization in the cytoplasm. Defective RNase ZS1 in tms5 plants leads to over-accumulation of UbL401, UbL402 and UbL404 mRNAs at restrictive but not permissive temperatures. Over-expression of UbL401 and UbL404 in wild-type plants caused male sterility, whereas knockdown of UbL401 and UbL404 in tms5 plants partially restored the male fertility at restrictive temperatures. Our results uncover a novel mechanism of RNase ZS1-mediated UbL40 mRNA decay which controls TGMS in rice and has potential applications not only of rice but also of other crops.
2016-08-01 | GSE42367 | GEO