MicroRNAs(miRNAs)have been demonstrated to control chicken skeletal muscle growth,however,the potential function of the miR-181-5p family in chicken myogenesis remains largely unknown.Here,our study identified the two...MicroRNAs(miRNAs)have been demonstrated to control chicken skeletal muscle growth,however,the potential function of the miR-181-5p family in chicken myogenesis remains largely unknown.Here,our study identified the two chicken(Gallus gallus;Gga)miR-181-5p family members widely expressed in various tissues,specifically miR-181a-5p and miR-181b-5p.Besides,the breast muscles of fast-growing broilers expressed higher levels of miR-181a-5p and miR-181b-5p than those of slow-growing layers.Functionally,miR-181a-5p and miR-181b-5p both promote the expression level of myogenic factors including myogenin(MyoG),myogenic differentiation 1(MyoD1),and myosin heavy chain(MyHC),meanwhile accelerating the myotube formation of skeletal muscle satellite cells(SMSCs).Mechanistically,miR-181a-5p and miR-181b-5p directly bind to the 3′untranslated region(UTR)of the transforming growth factor beta receptor 1(TGFBR1)mRNA,further reducing the expression of TGFBR1.TGFBR1 is a key Transforming growth factor beta(TGF-β)signaling transduction receptor and had a negative function in muscle cell differentiation.Furthermore,knockdown of TGFBR1 facilitated the expression of chicken myogenic factors,boosted myotube formation,and decreased the SMAD family member 2/3(SMAD2/3)phosphorylation in chicken SMSCs.SMAD2/3 are downstream of TGF-βsignaling,and miR-181a-5p and miR-181b-5p could reduce the expression of TGFBR1 to further diminish the SMAD2/3 phosphorylation.Our findings revealed that the miR-181-5p family targets TGFBR1 to break the TGF-βsignaling transduction,which resulted in promoting chicken skeletal muscle development.展开更多
目的对1例超声心动图提示为主动脉根部瘤及主动脉瓣关闭不全的患者进行基因检测,明确其可能的致病变异,为临床诊断和遗传咨询提供依据。方法应用二代测序技术对先证者进行全外显子组测序,重点分析主动脉瘤疾病及其他循环系统遗传病相关...目的对1例超声心动图提示为主动脉根部瘤及主动脉瓣关闭不全的患者进行基因检测,明确其可能的致病变异,为临床诊断和遗传咨询提供依据。方法应用二代测序技术对先证者进行全外显子组测序,重点分析主动脉瘤疾病及其他循环系统遗传病相关基因,应用Sanger测序对患者及家系成员的疑似致病位点进行检测。依据根据美国医学遗传学与基因组学学会(American College of Medical Geneticsand Genomics,ACMG)遗传变异分类标准与指南判定变异的致病性。结果二代测序结果显示患者的TGFBR1基因(NM_001130916.3)存在c.830T>C杂合变异,而家系正常成员均未检出该变异。SIFT.PolyPhen2和MutationTaster软件分析预测该变异为有害变异,可能导致编码蛋白结构和功能破坏。依据ACMG指南,该变异为可能致病(PM1+PM2+PM6+PP3+PP4)。结论TGFBR1基因c.830 T>C变异可能是该患者致病的原因,基因测序结果为临床诊断和遗传咨询提供了理论依据。展开更多
基金supported by the National Key Research and Development Program of China(2022YFF10002020)Sichuan Science and Technology Program,China(2021YFYZ0007 and 2021YFYZ0031).
文摘MicroRNAs(miRNAs)have been demonstrated to control chicken skeletal muscle growth,however,the potential function of the miR-181-5p family in chicken myogenesis remains largely unknown.Here,our study identified the two chicken(Gallus gallus;Gga)miR-181-5p family members widely expressed in various tissues,specifically miR-181a-5p and miR-181b-5p.Besides,the breast muscles of fast-growing broilers expressed higher levels of miR-181a-5p and miR-181b-5p than those of slow-growing layers.Functionally,miR-181a-5p and miR-181b-5p both promote the expression level of myogenic factors including myogenin(MyoG),myogenic differentiation 1(MyoD1),and myosin heavy chain(MyHC),meanwhile accelerating the myotube formation of skeletal muscle satellite cells(SMSCs).Mechanistically,miR-181a-5p and miR-181b-5p directly bind to the 3′untranslated region(UTR)of the transforming growth factor beta receptor 1(TGFBR1)mRNA,further reducing the expression of TGFBR1.TGFBR1 is a key Transforming growth factor beta(TGF-β)signaling transduction receptor and had a negative function in muscle cell differentiation.Furthermore,knockdown of TGFBR1 facilitated the expression of chicken myogenic factors,boosted myotube formation,and decreased the SMAD family member 2/3(SMAD2/3)phosphorylation in chicken SMSCs.SMAD2/3 are downstream of TGF-βsignaling,and miR-181a-5p and miR-181b-5p could reduce the expression of TGFBR1 to further diminish the SMAD2/3 phosphorylation.Our findings revealed that the miR-181-5p family targets TGFBR1 to break the TGF-βsignaling transduction,which resulted in promoting chicken skeletal muscle development.
文摘目的对1例超声心动图提示为主动脉根部瘤及主动脉瓣关闭不全的患者进行基因检测,明确其可能的致病变异,为临床诊断和遗传咨询提供依据。方法应用二代测序技术对先证者进行全外显子组测序,重点分析主动脉瘤疾病及其他循环系统遗传病相关基因,应用Sanger测序对患者及家系成员的疑似致病位点进行检测。依据根据美国医学遗传学与基因组学学会(American College of Medical Geneticsand Genomics,ACMG)遗传变异分类标准与指南判定变异的致病性。结果二代测序结果显示患者的TGFBR1基因(NM_001130916.3)存在c.830T>C杂合变异,而家系正常成员均未检出该变异。SIFT.PolyPhen2和MutationTaster软件分析预测该变异为有害变异,可能导致编码蛋白结构和功能破坏。依据ACMG指南,该变异为可能致病(PM1+PM2+PM6+PP3+PP4)。结论TGFBR1基因c.830 T>C变异可能是该患者致病的原因,基因测序结果为临床诊断和遗传咨询提供了理论依据。
