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Nucleic Acids Research Sep 2023MicroRNAs are sequentially processed by RNase III enzymes Drosha and Dicer. miR-451 is a highly conserved miRNA in vertebrates which bypasses Dicer processing and...
MicroRNAs are sequentially processed by RNase III enzymes Drosha and Dicer. miR-451 is a highly conserved miRNA in vertebrates which bypasses Dicer processing and instead relies on AGO2 for its maturation. miR-451 is highly expressed in erythrocytes and regulates the differentiation of erythroblasts into mature red blood cells. However, the mechanistic details underlying miR-451 biogenesis in erythrocytes remains obscure. Here, we report that the RNA binding protein CSDE1 which is required for the development of erythroblasts into erythrocytes, controls the expression of miR-451 in erythroleukemia cells. CSDE1 binds miR-451 and regulates AGO2 processing of pre-miR-451 through its N-terminal domains. CSDE1 further interacts with PARN and promotes the trimming of intermediate miR-451 to the mature length. Together, our results demonstrate that CSDE1 promotes biogenesis of miR-451 in erythroid progenitors.
Topics: Animals; MicroRNAs; Ribonuclease III; RNA-Binding Proteins; Humans
PubMed: 37493604
DOI: 10.1093/nar/gkad619 -
Wiley Interdisciplinary Reviews. RNA 2014Double-stranded(ds) RNA has diverse roles in gene expression and regulation, host defense, and genome surveillance in bacterial and eukaryotic cells. A central aspect of... (Review)
Review
Double-stranded(ds) RNA has diverse roles in gene expression and regulation, host defense, and genome surveillance in bacterial and eukaryotic cells. A central aspect of dsRNA function is its selective recognition and cleavage by members of the ribonuclease III (RNase III) family of divalent-metal-ion-dependent phosphodiesterases. The processing of dsRNA by RNase III family members is an essential step in the maturation and decay of coding and noncoding RNAs, including miRNAs and siRNAs. RNase III, as first purified from Escherichia coli, has served as a biochemically well-characterized prototype, and other bacterial orthologs provided the first structural information. RNase III family members share a unique fold (RNase III domain) that can dimerize to form a structure that binds dsRNA and cleaves phosphodiesters on each strand, providing the characteristic 2 nt, 3'-overhang product ends. Ongoing studies are uncovering the functions of additional domains, including, inter alia, the dsRNA-binding and PAZ domains that cooperate with the RNase III domain to select target sites, regulate activity, confer processivity, and support the recognition of structurally diverse substrates. RNase III enzymes function in multicomponent assemblies that are regulated by diverse inputs, and at least one RNase III-related polypeptide can function as a noncatalytic, dsRNA-binding protein. This review summarizes the current knowledge of the mechanisms of catalysis and target site selection of RNase III family members, and also addresses less well understood aspects of these enzymes and their interactions with dsRNA.
Topics: Animals; Humans; Models, Molecular; Protein Conformation; RNA, Double-Stranded; Ribonuclease III; Substrate Specificity
PubMed: 24124076
DOI: 10.1002/wrna.1195 -
Annual Review of Genetics 2013RNase III is a global regulator of gene expression in Escherichia coli that is instrumental in the maturation of ribosomal and other structural RNAs. We examine here how... (Review)
Review
RNase III is a global regulator of gene expression in Escherichia coli that is instrumental in the maturation of ribosomal and other structural RNAs. We examine here how RNase III itself is regulated in response to growth and other environmental changes encountered by the cell and how, by binding or processing double-stranded RNA (dsRNA) intermediates, RNase III controls the expression of genes. Recent insight into the mechanism of dsRNA binding and processing, gained from structural studies of RNase III, is reviewed. Structural studies also reveal new cleavage sites in the enzyme that can generate longer 3' overhangs.
Topics: 3' Untranslated Regions; 5' Untranslated Regions; Amino Acid Motifs; Bacteriophage lambda; Catalysis; Clustered Regularly Interspaced Short Palindromic Repeats; Escherichia coli; Escherichia coli Proteins; Eukaryotic Cells; Gene Expression Regulation, Bacterial; Nucleic Acid Conformation; Operon; Prokaryotic Cells; Protein Processing, Post-Translational; RNA; RNA Processing, Post-Transcriptional; RNA, Bacterial; RNA, Double-Stranded; RNA, Ribosomal; RNA, Small Untranslated; Ribonuclease III; Structure-Activity Relationship; Substrate Specificity; Virus Diseases
PubMed: 24274754
DOI: 10.1146/annurev-genet-110711-155618 -
International Journal of Molecular... Jan 2021Ribonuclease Dicer belongs to the family of RNase III endoribonucleases, the enzymes that specifically hydrolyze phosphodiester bonds found in double-stranded regions of... (Review)
Review
Ribonuclease Dicer belongs to the family of RNase III endoribonucleases, the enzymes that specifically hydrolyze phosphodiester bonds found in double-stranded regions of RNAs. Dicer enzymes are mostly known for their essential role in the biogenesis of small regulatory RNAs. A typical Dicer-type RNase consists of a helicase domain, a domain of unknown function (DUF283), a PAZ (Piwi-Argonaute-Zwille) domain, two RNase III domains, and a double-stranded RNA binding domain; however, the domain composition of Dicers varies among species. Dicer and its homologues developed only in eukaryotes; nevertheless, the two enzymatic domains of Dicer, helicase and RNase III, display high sequence similarity to their prokaryotic orthologs. Evolutionary studies indicate that a combination of the helicase and RNase III domains in a single protein is a eukaryotic signature and is supposed to be one of the critical events that triggered the consolidation of the eukaryotic RNA interference. In this review, we provide the genetic insight into the domain organization and structure of Dicer proteins found in vertebrate and invertebrate animals, plants and fungi. We also discuss, in the context of the individual domains, domain deletion variants and partner proteins, a variety of Dicers' functions not only related to small RNA biogenesis pathways.
Topics: Animals; Evolution, Molecular; Fungi; Gene Deletion; Humans; Models, Molecular; Plants; Protein Conformation; Protein Domains; Ribonuclease III
PubMed: 33435485
DOI: 10.3390/ijms22020616 -
Cancer Cytopathology Oct 2020
Topics: DEAD-box RNA Helicases; Humans; Mutation; Ribonuclease III; Thyroid Diseases
PubMed: 32897630
DOI: 10.1002/cncy.22327 -
Nature Communications Aug 2022Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital...
Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.
Topics: Animals; DEAD-box RNA Helicases; Female; Fertility; Kisspeptins; Male; Mice; MicroRNAs; Neurons; Ribonuclease III; Sexual Maturation
PubMed: 35945211
DOI: 10.1038/s41467-022-32347-4 -
Postepy Biochemii Oct 2019Endoribonuclease III Dicer plays a crucial role in the biogenesis of small regulatory RNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). However,... (Review)
Review
Endoribonuclease III Dicer plays a crucial role in the biogenesis of small regulatory RNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, this is not the only role that Dicer plays in cells. For example, it has been shown that Dicer is involved in processing of diverse classes of RNA, including tRNA and snoRNA, cleavage of repeat-element-derived RNAs, and maintenance of genome integrity. Dicer has also been found to participate in the chromosome fragmentation during apoptosis or in the inflammatory processes. Moreover, a recent discovery of Dicer-binding passive sites in mRNAs and long non-coding RNAs, and its putative nucleic acid chaperone activity, has pointed out a novel regulatory role of the enzyme. Here we focus on human Dicer and review its structure and function including recent findings on miRNA-independent roles and their impact on cell biology.
Topics: DNA Fragmentation; Humans; Molecular Chaperones; RNA Processing, Post-Transcriptional; RNA, Long Noncoding; RNA, Messenger; RNA, Small Untranslated; Ribonuclease III
PubMed: 31643164
DOI: 10.18388/pb.2019_267 -
Biochemical Society Transactions Aug 2014Endo-siRNAs (endogenous small-interfering RNAs) have recently emerged as versatile regulators of gene expression. They derive from double-stranded intrinsic transcripts... (Review)
Review
Endo-siRNAs (endogenous small-interfering RNAs) have recently emerged as versatile regulators of gene expression. They derive from double-stranded intrinsic transcripts and are processed by Dicer and associate with Argonaute proteins. In Caenorhabditis elegans, endo-siRNAs are known as 22G and 26G RNAs and are involved in genome protection and gene regulation. Drosophila melanogaster endo-siRNAs are produced with the help of specific Dicer and Argonaute isoforms and play an essential role in transposon control and the protection from viral infections. Biological functions of endo-siRNAs in vertebrates include repression of transposable elements and chromatin organization, as well as gene regulation at the transcriptional and post-transcriptional levels.
Topics: Animals; Argonaute Proteins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Drosophila melanogaster; RNA, Small Interfering; Ribonuclease III
PubMed: 25110021
DOI: 10.1042/BST20140068 -
Biochimie Nov 2011A well-defined mechanism governs the maturation of most microRNAs (miRNAs) in animals, via stepwise cleavage of precursor hairpin transcripts by the Drosha and Dicer... (Review)
Review
A well-defined mechanism governs the maturation of most microRNAs (miRNAs) in animals, via stepwise cleavage of precursor hairpin transcripts by the Drosha and Dicer RNase III enzymes. Recently, several alternative miRNA biogenesis pathways were elucidated, the most prominent of which substitutes Drosha cleavage with splicing. Such short hairpin introns are known as mirtrons, and their study has uncovered related pathways that combine splicing with other ribonucleolytic machinery to yield Dicer substrates for miRNA biogenesis. In this review, we consider the mechanisms of splicing-mediated miRNA biogenesis, computational strategies for mirtron discovery, and the evolutionary implications of the existence of multiple miRNA biogenesis pathways. Altogether, the features of mirtron pathways illustrate unexpected flexibility in combining RNA processing pathways, and highlight how multiple functions can be encoded by individual transcripts.
Topics: Animals; Base Sequence; Evolution, Molecular; Introns; MicroRNAs; Molecular Sequence Data; RNA Interference; RNA Precursors; RNA Processing, Post-Transcriptional; RNA Splicing; RNA, Untranslated; Ribonuclease III
PubMed: 21712066
DOI: 10.1016/j.biochi.2011.06.017 -
Pflugers Archiv : European Journal of... Jun 2016MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for the biogenesis of small RNAs guiding post-transcriptional repression. Requirements for... (Review)
Review
MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for the biogenesis of small RNAs guiding post-transcriptional repression. Requirements for Dicer activity differ in the two pathways. The biogenesis of miRNAs requires a single Dicer cleavage of a short hairpin precursor to produce a small RNA with a precisely defined sequence, while small RNAs in RNAi come from a processive cleavage of a long double-stranded RNA (dsRNA) into a pool of small RNAs with different sequences. While Dicer is generally conserved among eukaryotes, its substrate recognition, cleavage, and biological roles differ. In Metazoa, a single Dicer can function as a universal factor for RNAi and miRNA pathways or as a factor adapted specifically for one of the pathways. In this review, we focus on the structure, function, and evolution of mammalian Dicer. We discuss key structural features of Dicer and other factors defining Dicer substrate repertoire and biological functions in mammals in comparison with invertebrate models. The key for adaptation of Dicer for miRNA or RNAi pathways is the N-terminal helicase, a dynamically evolving Dicer domain. Its functionality differs between mammals and invertebrates: the mammalian Dicer is well adapted to produce miRNAs while its ability to support RNAi is limited.
Topics: Animals; Evolution, Molecular; Humans; MicroRNAs; Ribonuclease III
PubMed: 27048428
DOI: 10.1007/s00424-016-1817-6