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@proceedings{1862096, author = {Zapletal, David and Kubíček, Karel and Zánová, Martina and Malik, Radek and Šebesta, Marek and Nováček, Jiří and Svoboda, Petr and Štefl, Richard}, booktitle = {Instruct Biennial Structural Biology ConferenceMuntgebouw, Utrecht, The Netherlands | 19-20 May, 2022}, keywords = {Dicer; RNA interference; RNAi; miRNA; siRNA}, language = {eng}, title = {Cryo-EM reveals the structural basis for the regulatory function of HEL1 domain in vertebrate DICERs}, year = {2022} }
TY - CONF ID - 1862096 AU - Zapletal, David - Kubíček, Karel - Zánová, Martina - Malik, Radek - Šebesta, Marek - Nováček, Jiří - Svoboda, Petr - Štefl, Richard PY - 2022 TI - Cryo-EM reveals the structural basis for the regulatory function of HEL1 domain in vertebrate DICERs KW - Dicer KW - RNA interference KW - RNAi KW - miRNA KW - siRNA N2 - Dicer is RNase III enzyme producing small RNA in RNA silencing pathways. In mice, there are two isoforms that differ by presence or absence of the N-terminal HEL1 domain. The full-length Dicer acts in microRNA (miRNA) biogenesis while the truncated version, present in oocytes (DicerO), generates small interfering RNAs (siRNA) in RNA interference (RNAi) pathway. While models for siRNA and miRNA processing by vertebrate Dicer have emerged from the structural and biochemical studies, the active dicing state in Dicer-RNA structures has not been structurally characterized yet. In this study we used cryo-electron microscopy, AI-based prediction, and biochemical approaches to understand the structural difference between Dicer and DicerO, explaining their different in vivo functions. We observed that Dicer-RNA complex exists prevalently in an inactive, pre-dicing state (Fig.1b), while DicerO-RNA was observed almost exclusively in dicing-state (Fig.2c), revealing the molecular principles of substrate selection and enzymatic activity. Our data suggest HEL1 role in Dicer activity and substrate specificity by regulation of the loading of RNA substrate. ER -
ZAPLETAL, David, Karel KUBÍČEK, Martina ZÁNOVÁ, Radek MALIK, Marek ŠEBESTA, Jiří NOVÁČEK, Petr SVOBODA and Richard ŠTEFL. Cryo-EM reveals the structural basis for the regulatory function of HEL1 domain in vertebrate DICERs. In \textit{Instruct Biennial Structural Biology ConferenceMuntgebouw, Utrecht, The Netherlands $|$ 19-20 May, 2022}. 2022.
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