The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of B...The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.展开更多
Adenosine to inosine （A-to-I） RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA （...Adenosine to inosine （A-to-I） RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA （ADAR） proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions （UTRs） and introns are located in pre-rnRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degrada- tion, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA （miRNA）, small interfering RNA （siRNA） and long non-coding RNA （lncRNA） are related to pre-mRNA splicing, translation, and gene regulation. A-to-I edit- ing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions （UTRs and introns） and non-coding RNAs （miRNA, siRNA, and IncRNA）.展开更多
In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a ne...In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.展开更多
MicroRNAs（miRNAs）constitute a class of small non-coding RNAs that participate in various biological processes by repressing protein translation or destabilizing target mRNAs.miRNA biogenesis begins with the transcri...MicroRNAs（miRNAs）constitute a class of small non-coding RNAs that participate in various biological processes by repressing protein translation or destabilizing target mRNAs.miRNA biogenesis begins with the transcription of primary miRNAs（pri-miRNAs）in the cell nucleus,which are then cleaved by the Drosha/DGCR complex into precursor miRNAs（pre-miRNAs）.The pre-miRNAs are transported by exportin-5（XPO5）from the nucleus to the cytoplasm,展开更多
文摘The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.
基金supported by the National Natural Science Foundation of China(31125011,31071148,31270844)the Doctoral Foundation of Ministry of Education of China(20110101130012)Postdoctoral Research Project of Zhejiang Province(BSH1302085)
文摘Adenosine to inosine （A-to-I） RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA （ADAR） proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions （UTRs） and introns are located in pre-rnRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degrada- tion, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA （miRNA）, small interfering RNA （siRNA） and long non-coding RNA （lncRNA） are related to pre-mRNA splicing, translation, and gene regulation. A-to-I edit- ing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions （UTRs and introns） and non-coding RNAs （miRNA, siRNA, and IncRNA）.
基金supported by National Natural Science Foundation of China (81530042, 31571529, 31210103905, 31571519, 31571390, 31371510, 31301208, 31471250, 31401257)the Ministry of Science and Technology (2012CB966603, 2013CB967600, 2013CB967401)+2 种基金Science and Technology Commission of Shanghai Municipality (15JC1403200, 15JC1403201)Shanghai Rising-Star Program (14QA1403900)the Fundamental Research Funds for the Central Universities (2000219099)
文摘In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.
文摘MicroRNAs（miRNAs）constitute a class of small non-coding RNAs that participate in various biological processes by repressing protein translation or destabilizing target mRNAs.miRNA biogenesis begins with the transcription of primary miRNAs（pri-miRNAs）in the cell nucleus,which are then cleaved by the Drosha/DGCR complex into precursor miRNAs（pre-miRNAs）.The pre-miRNAs are transported by exportin-5（XPO5）from the nucleus to the cytoplasm,
