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Structure of the human DICER-pre-miRNA complex in a dicing state I

ABSTRACT: Structure of the human DICER-pre-miRNA complex in a dicing state I

PROVIDER: PRJNA838376 | ENA |

REPOSITORIES: ENA

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Structure of the human DICER-pre-miRNA complex in a dicing state I

Project description:Dicer plays a key role in small RNA biogenesis by processing double-stranded RNAs (dsRNAs). Human DICER (hDICER) is specialized in processing of small hairpins such as pre-microRNAs (pre-miRNAs) with a limited activity towards long dsRNAs, unlike its homologs in lower eukaryotes and plants which cleave long dsRNAs. While the mechanism of long dsRNA cleavage has been well documented, our understanding of pre-miRNA processing is limited due to lack of the structure of hDICER in a catalytic state. Here we report the cryo-electron microscopy structure of hDICER bound to pre-miRNA in a dicing state, uncovering the structural basis for pre-miRNA processing.

2022-11-23 | GSE203062 | GEO

Structure of the human DICER-pre-miRNA complex in a dicing state II

2022-11-23 | GSE215866 | GEO

Structure of the human DICER-pre-miRNA complex in a dicing state

Project description:Structure of the human DICER-pre-miRNA complex in a dicing state

| PRJNA891056 | ENA

Structure of the human DICER-pre-miRNA complex in a dicing state II

Project description:Structure of the human DICER-pre-miRNA complex in a dicing state II

| PRJNA891057 | ENA

Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation

Project description:In eukaryotes, small RNAs (sRNAs) play critical roles in multiple biological processes. Dicer endonucleases are central to sRNA biogenesis. In plants, DICER-LIKE PROTEIN 3 (DCL3) produces 24-nt small interfering RNAs (siRNAs) that determine the specificity of the RNA-directed DNA methylation (RdDM) pathway. Here, we determined structure of a DCL3-pre-siRNA complex in an active dicing-competent state. The 5′-phosphorylated-A1 of the guide strand and the 1-nt 3′-overhang of the complementary strand are specifically recognized by a positively charged pocket and an aromatic cap, respectively. The 24-nt siRNA length dependence relies on the separation between the 5′-phosphorylated-end of the guide RNA and dual cleavage sites formed by the paired RNaseIII domains. These structural studies, complemented by functional data, reveal insights into the dicing principle for Dicers in general.

2021-10-14 | GSE179616 | GEO

Structure of the human DICER-pre-miRNA complex in a dicing state

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-11-23 | GSE215867 | GEO

Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation

Project description:Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation

| PRJNA744279 | ENA

A sliding-bulge structure at the Dicer processing site of pre-miRNA regulates alternative Dicer processing to generate 5’-isomiRs (pre-miR-203)

Project description:5’-isomiRs expand the repertoire of miRNA targets. However, how they are generated is not well understood. Here, we showed that, for some miRNAs in mammalian cells, 5’-isomiRs are generated by alternative Dicer processing by using miRNA offset RNAs (moRs) to determine Drosha cleavage sites in cells. In addition, we showed that in miR-203, alternative Dicer processing is regulated by a conserved sliding-bulge structure at the Dicer processing site, which allows the pre-miRNA molecule to fold into two different structures that are processed differently by Dicer. So far no RNA motif that slides to change conformation and alter a protein–RNA interaction has been reported. Thus, our study revealed a novel RNA motif that regulates 5’-isomiR generation in some miRNAs. It might also contribute to regulating protein–RNA interactions in other biological processes, since it takes only one point mutation to generate the sliding bulge, and there are a large number of different RNAs in the cell.

2016-09-01 | GSE80771 | GEO

A sliding-bulge structure at the Dicer processing site of pre-miRNA regulates alternative Dicer processing to generate 5’-isomiRs (miR-203)

2016-09-01 | GSE80772 | GEO

Determinants of selectivity in the dicing mechanism

Project description:The RNase III enzyme, DICER, is instrumental in the production of small RNAs, including miRNAs and siRNAs, by cleaving their precursors, such as pre-miRNAs, shRNAs, and long duplex RNAs. Utilizing High-throughput (HT) cleavage assays, our study delves into the cleavage activity of DICER. We challenge the widely accepted 2-nt loop counting rule in the previous study, revealing a divergent mechanism, the bipartite base pairing rule. This rule directs DICER's cleavage sites via the RNase III domain. Moreover, we demystify the recognition mechanism of the previously identified YCR motif. Building on this understanding, a secondary YCR motif that also influences DICER's cleavage sites has been discovered. We also address a long-debated issue concerning DICER's cleavage sites on long stem RNAs, such as pre-siRNAs or long shRNAs/pre-miRNAs. Our study shows that the dsRBD plays a crucial role in determining the cleavage sites of DICER in long-stem RNAs. In sum, our research provides a comprehensive understanding of several fundamental DICER mechanisms, challenging the long-standing model of the loop counting rule. This newfound knowledge reshapes our understanding of DICER's mechanisms, providing a robust foundation for future studies investigating the vast number of DICER mutations linked to various diseases.

2024-06-01 | GSE252434 | GEO

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