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A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective

The RNA interference pathway (RNAi) is executed by two core enzymes, Dicer and Argonaute, for accomplishing a tailored transcriptional and post-transcriptional gene regulation. Dicer, an RNase III enzyme, initiates the RNAi pathway, plays a pivotal role in fighting infection against pathogens, and a...

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Autores principales: Paturi, Sneha, Deshmukh, Mandar V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138440/
https://www.ncbi.nlm.nih.gov/pubmed/34026825
http://dx.doi.org/10.3389/fmolb.2021.643657
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author Paturi, Sneha
Deshmukh, Mandar V.
author_facet Paturi, Sneha
Deshmukh, Mandar V.
author_sort Paturi, Sneha
collection PubMed
description The RNA interference pathway (RNAi) is executed by two core enzymes, Dicer and Argonaute, for accomplishing a tailored transcriptional and post-transcriptional gene regulation. Dicer, an RNase III enzyme, initiates the RNAi pathway, plays a pivotal role in fighting infection against pathogens, and acts as a housekeeping enzyme for cellular homeostasis. Here, we review structure-based functional insights of Dicer and its domains present in a diverse group of organisms. Although Dicer and its domains are evolutionarily conserved from microsporidian parasites to humans, recent cryo-electron microscopy structures of Homo sapiens Dicer and Drosophila melanogaster Dicer-2 suggest characteristic variations in the mechanism of the dsRNA substrate recognition. Interestingly, the necessity for more than one functionally distinct Dicer paralogs in insects and plants compared with a single Dicer in other eukaryotic life forms implies Dicer’s role in the interplay of RNAi and other defense mechanisms. Based on the structural and mechanistic information obtained during the last decade, we aim to highlight the significance of key Dicer domains that are crucial to Dicer specific recognition and precise cleavage of dsRNA substrates. Further, the role of Dicer in the formation of Argonaute-based RNA-induced silencing complex (RISC) assembly formation, Dicer’s ability to regulate a complex protein interaction network, and its role in other cellular processes, as well as its therapeutic potentials, are emphasized.
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spelling pubmed-81384402021-05-22 A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective Paturi, Sneha Deshmukh, Mandar V. Front Mol Biosci Molecular Biosciences The RNA interference pathway (RNAi) is executed by two core enzymes, Dicer and Argonaute, for accomplishing a tailored transcriptional and post-transcriptional gene regulation. Dicer, an RNase III enzyme, initiates the RNAi pathway, plays a pivotal role in fighting infection against pathogens, and acts as a housekeeping enzyme for cellular homeostasis. Here, we review structure-based functional insights of Dicer and its domains present in a diverse group of organisms. Although Dicer and its domains are evolutionarily conserved from microsporidian parasites to humans, recent cryo-electron microscopy structures of Homo sapiens Dicer and Drosophila melanogaster Dicer-2 suggest characteristic variations in the mechanism of the dsRNA substrate recognition. Interestingly, the necessity for more than one functionally distinct Dicer paralogs in insects and plants compared with a single Dicer in other eukaryotic life forms implies Dicer’s role in the interplay of RNAi and other defense mechanisms. Based on the structural and mechanistic information obtained during the last decade, we aim to highlight the significance of key Dicer domains that are crucial to Dicer specific recognition and precise cleavage of dsRNA substrates. Further, the role of Dicer in the formation of Argonaute-based RNA-induced silencing complex (RISC) assembly formation, Dicer’s ability to regulate a complex protein interaction network, and its role in other cellular processes, as well as its therapeutic potentials, are emphasized. Frontiers Media S.A. 2021-05-07 /pmc/articles/PMC8138440/ /pubmed/34026825 http://dx.doi.org/10.3389/fmolb.2021.643657 Text en Copyright © 2021 Paturi and Deshmukh. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Paturi, Sneha
Deshmukh, Mandar V.
A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
title A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
title_full A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
title_fullStr A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
title_full_unstemmed A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
title_short A Glimpse of “Dicer Biology” Through the Structural and Functional Perspective
title_sort glimpse of “dicer biology” through the structural and functional perspective
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138440/
https://www.ncbi.nlm.nih.gov/pubmed/34026825
http://dx.doi.org/10.3389/fmolb.2021.643657
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