Almost all pre-miRNAs in eukaryotic cytoplasm are recognized and processed into double-stranded microRNAs by the endonuclease Dicer protein comprising of multiple domains. As a key player in the small RNA induced gene...Almost all pre-miRNAs in eukaryotic cytoplasm are recognized and processed into double-stranded microRNAs by the endonuclease Dicer protein comprising of multiple domains. As a key player in the small RNA induced gene silencing pathway, the major domains of Dicer are conserved among different species with the exception of the N-terminal components. Human Dicer＇s N-terminal domain has been shown to play an autoinhibitory function of the protein＇s dicing activity. Such an auto-inhibition can be released when the human Dicer protein dimerizes with its partner protein, such as TRBP, PACT through the N-terminal DExH/D （ATPase- helicase） domain. The typical feature of a pre-miRNA contains a terminal loop and a stem duplex, which bind to human Dicer＇s DExH/D （ATPase-helicase） domain and PAZ domain respectively during the dicing reaction. Here, we show that pre-miRNA＇s terminal loop can regulate human Dicer＇s enzymatic activity by interacting with the DExH/D （ATPase-helicase） domain. We found that various editing products of pre-miR-151 by the ADAR1P110 protein, an A-to-I editing enzyme that modifies pre-miRNAs sequence, have different terminal loop structures and different activity regulatory effects on human Dicer. Single particle electron microscopy reconstruction revealed that pre-miRNAs with different terminal loop structures induce human Dicer＇s DExH/D （ATPase-helicase） domain into different conformational states, in correlation with their activity regulatory effects.展开更多
A-to-I RNA editing, the important event of gene modification, which takes place at post-transcriptional level, was firstly reported in 1991. The molecular mechanism of A-to-I RNA editing involves site-selective deamin...A-to-I RNA editing, the important event of gene modification, which takes place at post-transcriptional level, was firstly reported in 1991. The molecular mechanism of A-to-I RNA editing involves site-selective deamination of adenosine to inosine in pre-mRNA, which leads to altering translation codons and splicing in nuclear transcripts, thereby functionally distinct proteins can be produced from a single gene. The mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely expressed in brain and other tissues, however, up to date their sub-strates are mainly found in the central nervous system. It has recently been noticed that imperfect editing of these RNA substrates play critical roles in corresponding diseases, indi-cating that A-to-I RNA editing may be quite important in physiological or pathophysiological processes. Finding more new substrates of ADARs, especially in peripheral tissues, and performing functional research on new genes will be helpful to elucidate the biological significance of A-to-I RNA editing.展开更多
A-to-I RNA editing, the important event of gene modification, which takes place at post-transcriptional level, was firstly reported in 1991. The molecular mechanism of A-to-I RNA editing involves site-selective deamin...A-to-I RNA editing, the important event of gene modification, which takes place at post-transcriptional level, was firstly reported in 1991. The molecular mechanism of A-to-I RNA editing involves site-selective deamination of adenosine to inosine in pre-mRNA, which leads to altering translation codons and splicing in nuclear transcripts, thereby functionally distinct proteins can be produced from a single gene. The mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely expressed in brain and other tissues, however, up to date their substrates are mainly found in the central nervous system. It has recently been noticed that imperfect editing of these RNA substrates play critical roles in corresponding diseases, indicating that A-to-I RNA editing may be quite important in physiological or pathophysiological processes. Finding more new substrates of ADARs, especially in peripheral tissues, and performing functional research on new genes will be helpful to elucidate the biological significance of A-to-I RNA editing.展开更多
文摘Almost all pre-miRNAs in eukaryotic cytoplasm are recognized and processed into double-stranded microRNAs by the endonuclease Dicer protein comprising of multiple domains. As a key player in the small RNA induced gene silencing pathway, the major domains of Dicer are conserved among different species with the exception of the N-terminal components. Human Dicer＇s N-terminal domain has been shown to play an autoinhibitory function of the protein＇s dicing activity. Such an auto-inhibition can be released when the human Dicer protein dimerizes with its partner protein, such as TRBP, PACT through the N-terminal DExH/D （ATPase- helicase） domain. The typical feature of a pre-miRNA contains a terminal loop and a stem duplex, which bind to human Dicer＇s DExH/D （ATPase-helicase） domain and PAZ domain respectively during the dicing reaction. Here, we show that pre-miRNA＇s terminal loop can regulate human Dicer＇s enzymatic activity by interacting with the DExH/D （ATPase-helicase） domain. We found that various editing products of pre-miR-151 by the ADAR1P110 protein, an A-to-I editing enzyme that modifies pre-miRNAs sequence, have different terminal loop structures and different activity regulatory effects on human Dicer. Single particle electron microscopy reconstruction revealed that pre-miRNAs with different terminal loop structures induce human Dicer＇s DExH/D （ATPase-helicase） domain into different conformational states, in correlation with their activity regulatory effects.
文摘A-to-I RNA editing, the important event of gene modification, which takes place at post-transcriptional level, was firstly reported in 1991. The molecular mechanism of A-to-I RNA editing involves site-selective deamination of adenosine to inosine in pre-mRNA, which leads to altering translation codons and splicing in nuclear transcripts, thereby functionally distinct proteins can be produced from a single gene. The mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely expressed in brain and other tissues, however, up to date their sub-strates are mainly found in the central nervous system. It has recently been noticed that imperfect editing of these RNA substrates play critical roles in corresponding diseases, indi-cating that A-to-I RNA editing may be quite important in physiological or pathophysiological processes. Finding more new substrates of ADARs, especially in peripheral tissues, and performing functional research on new genes will be helpful to elucidate the biological significance of A-to-I RNA editing.
文摘A-to-I RNA editing, the important event of gene modification, which takes place at post-transcriptional level, was firstly reported in 1991. The molecular mechanism of A-to-I RNA editing involves site-selective deamination of adenosine to inosine in pre-mRNA, which leads to altering translation codons and splicing in nuclear transcripts, thereby functionally distinct proteins can be produced from a single gene. The mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely expressed in brain and other tissues, however, up to date their substrates are mainly found in the central nervous system. It has recently been noticed that imperfect editing of these RNA substrates play critical roles in corresponding diseases, indicating that A-to-I RNA editing may be quite important in physiological or pathophysiological processes. Finding more new substrates of ADARs, especially in peripheral tissues, and performing functional research on new genes will be helpful to elucidate the biological significance of A-to-I RNA editing.
