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

Abstract

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.

Are Metabolites From the Gut Microbiota Capable of Regulating Epigenetic Mechanisms in the Human Parasite Entamoeba histolytica?

“…DICER and RISC complex are used in the first two methods ( Paturi and Deshmukh, 2021 ). Despite lacking a gene matching the canonical Dicer structure, E. histolytica does express an RnaseIII protein (EHI_068740) ( Abed and Ankri, 2005 ; Pompey et al, 2015 ).…”

State of Drosophila melanogaster Ovaries after a Full Cycle of Gametogenesis under Microgravity Modeling: Cellular Respiration and the Content of Cytoskeletal Proteins

“…Since DNA methylation in Drosophila is described but is not widely researched [32], and the RNA interference mechanism predominantly leads to the elimination of foreign/aberrant RNA [33,34], we decided to analyze the posttranslational modifications of histones, primarily the acetylation of histone H3, as one of the main participants in the regulation of gene expression due to its position in the nucleosoma.…”

miR-218: A Stress-Responsive Epigenetic Modifier

“…Mammalian miRNA biogenesis follows a programmed pathway to produce the mature effector molecule mediated by two ribonuclease (RNase) III enzymes, Drosha and Dicer [ 15 ]. First, miRNAs are converted to precursor transcripts (pre-miRNA) from primary miRNAs by Drosha, a nuclear RNase III enzyme, which is then exported to cytosol and processed by the RNase III enzyme Dicer [ 38 , 39 ]. Drosha is part of a multiprotein complex, the microprocessor, which mediates the nuclear processing of the primary miRNAs into stem-loop precursors of approximately 60 to 70 nucleotides (pre-miRNA).…”