Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome(PCOS)and androgen receptor(AR)in ovarian granulosa cells(GCs)functions as an important element to the accumulation of androgens.This ...Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome(PCOS)and androgen receptor(AR)in ovarian granulosa cells(GCs)functions as an important element to the accumulation of androgens.This study verified the existence of alternative splicing variant of AR(AR-SVs)in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs.And compared to the normal individuals,the expression of Serine/arginine-rich splicing factor 2(SRSF2)was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs.More importantly,we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183,and testostrone(T)concentrations in the culture medium were increased.The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated,while the expression of AR significantly increased;however,the function of AR was also inhibited when T concentration in the culture medium was increased.This study has proved that SRSFs are regulated by corresponding miRNAs,and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR,leading to the accumulation of androgens in the ovary.展开更多
Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize di...Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.展开更多
人类基因中约有94％发生选择性剪接，使同一前体 m R‐NA分子产生不同基因型，编码不同蛋白质，极大增加了基因表达复杂程度和蛋白质多样性［1］。不同组织出现疾病时显示特定模式剪接变异体，这些剪接模式依赖于剪接因子在细胞核中的...人类基因中约有94％发生选择性剪接，使同一前体 m R‐NA分子产生不同基因型，编码不同蛋白质，极大增加了基因表达复杂程度和蛋白质多样性［1］。不同组织出现疾病时显示特定模式剪接变异体，这些剪接模式依赖于剪接因子在细胞核中的相对表达，包括表达量或翻译后修饰［2］。富含丝氨酸／精氨酸剪接因子1（SRSF1），是1个典型富含丝氨酸／精氨酸SR蛋白家族成员，参与基因组成性剪接和选择性剪接［3］。SRSF1通过调节基因选择性剪接参与肿瘤形成发展。展开更多
文摘Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome(PCOS)and androgen receptor(AR)in ovarian granulosa cells(GCs)functions as an important element to the accumulation of androgens.This study verified the existence of alternative splicing variant of AR(AR-SVs)in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs.And compared to the normal individuals,the expression of Serine/arginine-rich splicing factor 2(SRSF2)was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs.More importantly,we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183,and testostrone(T)concentrations in the culture medium were increased.The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated,while the expression of AR significantly increased;however,the function of AR was also inhibited when T concentration in the culture medium was increased.This study has proved that SRSFs are regulated by corresponding miRNAs,and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR,leading to the accumulation of androgens in the ovary.
文摘Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.
文摘人类基因中约有94％发生选择性剪接，使同一前体 m R‐NA分子产生不同基因型，编码不同蛋白质，极大增加了基因表达复杂程度和蛋白质多样性［1］。不同组织出现疾病时显示特定模式剪接变异体，这些剪接模式依赖于剪接因子在细胞核中的相对表达，包括表达量或翻译后修饰［2］。富含丝氨酸／精氨酸剪接因子1（SRSF1），是1个典型富含丝氨酸／精氨酸SR蛋白家族成员，参与基因组成性剪接和选择性剪接［3］。SRSF1通过调节基因选择性剪接参与肿瘤形成发展。
