N6-methyladenosine(m6A)plays a key role in mammalian early embryonic development and cell lineage differentiation.However,the role and mechanisms of 18S ribosomal RNA(rRNA)m6A methyltransferase METTL5 in early embryon...N6-methyladenosine(m6A)plays a key role in mammalian early embryonic development and cell lineage differentiation.However,the role and mechanisms of 18S ribosomal RNA(rRNA)m6A methyltransferase METTL5 in early embryonic development remain unclear.Here,we found that 18S rRNA m6A methyltransferase METTL5 plays an important role in porcine early embryonic development.METTL5 knockdown and overexpression significantly reduced the developmental efficiency of porcine early embryos and impaired cell lineage allocation.METTL5 knockdown apparently decreased the global translation efficiency in blastocyst,while METTL5 overexpression increased the global translation efficiency.Furthermore,METTL5 knockdown did not affect the abundance of CDX2 mRNA,but resulted in a significant reduction in CDX2 protein levels.Moreover,the low developmental efficiency and abnormal lineage distribution of METTL5 knockdown embryos could be rescued by CDX2 overexpression.Collectively,our results demonstrated that 18S rRNA methyltransferase METTL5 regulates porcine early embryonic development via modulating the translation of CDX2.展开更多
目的研究急性髓系白血病(AML)患者CDX2与β-catenin基因表达的相关性。方法实时定量PCR方法检测92例初诊AML、30例非恶性血液病患者(对照)CDX2及β-catenin m RNA表达,Western blot检测其中的26例AML、8例非恶性血液病患者CDX2、β-cate...目的研究急性髓系白血病(AML)患者CDX2与β-catenin基因表达的相关性。方法实时定量PCR方法检测92例初诊AML、30例非恶性血液病患者(对照)CDX2及β-catenin m RNA表达,Western blot检测其中的26例AML、8例非恶性血液病患者CDX2、β-catenin蛋白表达。结果 AML组CDX2 m RNA和蛋白表达阳性率分别为84.78%和76.92%,对照组未检测到表达(P<0.01);β-catenin m RNA和蛋白在两组均表达,但AML组显著高于对照组(P<0.01)。CDX2、β-catenin m RNA表达均与初诊时白细胞数、LDH水平呈正相关(P<0.01)。AML患者获得完全缓解时,CDX2 m RNA转阴、β-catenin m RNA表达显著下降,复发时两者均增高。AML患者CDX2与β-catenin无论在m RNA和蛋白水平表达均呈显著正相关(P<0.01)。结论 AML患者存在CDX2基因过表达及Wnt/β-catenin信号通路激活,且CDX2与β-catenin表达呈显著正相关。展开更多
基金supported by grants from the Sub-project of National Key Research and Development Program of China(2021YFA0805905-1)the Special Fund for Anhui Agriculture Research System,China(AHCYJSTX-04)+2 种基金the Joint Research Project on the Anhui Local Pigs Breeding and Utilization,China(340000211260001000431)the Open Project of Key Laboratory of Embryo Development and Reproductive Regulation of Anhui Province,China(FSKFKT004)the Major Special Science And Technology Project of Anhui Province,China(202103a06020013)。
文摘N6-methyladenosine(m6A)plays a key role in mammalian early embryonic development and cell lineage differentiation.However,the role and mechanisms of 18S ribosomal RNA(rRNA)m6A methyltransferase METTL5 in early embryonic development remain unclear.Here,we found that 18S rRNA m6A methyltransferase METTL5 plays an important role in porcine early embryonic development.METTL5 knockdown and overexpression significantly reduced the developmental efficiency of porcine early embryos and impaired cell lineage allocation.METTL5 knockdown apparently decreased the global translation efficiency in blastocyst,while METTL5 overexpression increased the global translation efficiency.Furthermore,METTL5 knockdown did not affect the abundance of CDX2 mRNA,but resulted in a significant reduction in CDX2 protein levels.Moreover,the low developmental efficiency and abnormal lineage distribution of METTL5 knockdown embryos could be rescued by CDX2 overexpression.Collectively,our results demonstrated that 18S rRNA methyltransferase METTL5 regulates porcine early embryonic development via modulating the translation of CDX2.
文摘目的研究急性髓系白血病(AML)患者CDX2与β-catenin基因表达的相关性。方法实时定量PCR方法检测92例初诊AML、30例非恶性血液病患者(对照)CDX2及β-catenin m RNA表达,Western blot检测其中的26例AML、8例非恶性血液病患者CDX2、β-catenin蛋白表达。结果 AML组CDX2 m RNA和蛋白表达阳性率分别为84.78%和76.92%,对照组未检测到表达(P<0.01);β-catenin m RNA和蛋白在两组均表达,但AML组显著高于对照组(P<0.01)。CDX2、β-catenin m RNA表达均与初诊时白细胞数、LDH水平呈正相关(P<0.01)。AML患者获得完全缓解时,CDX2 m RNA转阴、β-catenin m RNA表达显著下降,复发时两者均增高。AML患者CDX2与β-catenin无论在m RNA和蛋白水平表达均呈显著正相关(P<0.01)。结论 AML患者存在CDX2基因过表达及Wnt/β-catenin信号通路激活,且CDX2与β-catenin表达呈显著正相关。
