A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the<i>let-7</i>Small Temporal RNA

Hutvágner, György; McLachlan, Juanita; Pasquinelli, Amy E.; Bálint, Éva; Tuschl, Thomas; Zamore, Phillip D.

doi:10.1126/science.1062961

Cited by 2,482 publications

(1,612 citation statements)

References 32 publications

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“…Drosha endonucleolytically cleaves out the stem-loop structure, the precursor-miRNA (pre-miRNA), which is exported out of the nucleus by Exportin-5 [14]. In the cytoplasm, another RNase III-like enzyme, Dicer, processes the pre-miRNA to mature miRNAs [15,16]. In contrast, in plants both cleavage steps take place in the nucleus [17,18].…”

Section: Introductionmentioning

confidence: 99%

Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum

et al. 2018

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Micro (mi)RNAs regulate gene expression in many eukaryotic organisms where they control diverse biological processes. Their biogenesis, from primary transcripts to mature miRNAs, have been extensively characterized in animals and plants, showing distinct differences between these phylogenetically distant groups of organisms. However, comparably little is known about miRNA biogenesis in organisms whose evolutionary position is placed in between plants and animals and/or in unicellular organisms. Here, we investigate miRNA maturation in the unicellular amoeba Dictyostelium discoideum, belonging to Amoebozoa, which branched out after plants but before animals. High-throughput sequencing of small RNAs and poly(A)-selected RNAs demonstrated that the Dicer-like protein DrnB is required, and essentially specific, for global miRNA maturation in D. discoideum. Our RNA-seq data also showed that longer miRNA transcripts, generally preceded by a T-rich putative promoter motif, accumulate in a drnB knock-out strain. For two model miRNAs we defined the transcriptional start sites (TSSs) of primary (pri)-miRNAs and showed that they carry the RNA polymerase II specific m7G-cap. The generation of the 3ʹ-ends of these pri-miRNAs differs, with pri-mir-1177 reading into the downstream gene, and pri-mir-1176 displaying a distinct end. This 3´-end is processed to shorter intermediates, stabilized in DrnB-depleted cells, of which some carry a short oligo(A)-tail. Furthermore, we identified 10 new miRNAs, all DrnB dependent and developmentally regulated. Thus, the miRNA machinery in D. discoideum shares features with both plants and animals, which is in agreement with its evolutionary position and perhaps also an adaptation to its complex lifestyle: unicellular growth and multicellular development.

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Section: Introductionmentioning

confidence: 99%

Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum

et al. 2018

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“…The Droshagenerated pre-miRNA is a 70-to 80-nt RNA with a typical stem-loop structure. It is transported to the cytoplasm by Exportin-5 (Yi et al, 2003;Lund et al, 2004) where it is processed by another RNaseIII type protein, Dicer, to generate the mature (20-to 22-nt) miRNA (Grishok et al, 2001;Hutvagner et al, 2001;Ketting et al, 2001;Knight and Bass, 2001). miRNAs have partially complementary sequences to certain mRNAs and guide a protein complex, RISC (RNA induced silencing complex), to the target mRNAs (Khvorova et al, 2003;Schwarz et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

FGF‐4 signaling is involved in mir‐206 expression in developing somites of chicken embryos

Sweetman

Rathjen

Jefferson

et al. 2006

Developmental Dynamics

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The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs. Developmental Dynamics 235:2185-2191, 2006.

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“…The pre‐miRNA is then exported to the cytoplasm using exportin 5 and the small Ran GTPase (Bohnsack, Czaplinski & Gorlich, 2004; Yi, Qin, Macara & Cullen, 2003). In the cytoplasm, the pre‐miRNA is therefore cleaved by the endonuclease Dicer into a ≈ 25 nt duplex miRNA (Hutvágner et al., 2001). This duplex is bound by the Argonaute protein (AGO) in a complex called “RNA‐induced silencing complex” (RISC), which eliminates one strand of the duplex to conserve the guide strand corresponding to the mature ≈25 nt miRNA (Kobayashi & Tomari, 2016).…”

Section: Micrornasmentioning

confidence: 99%

MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies

et al. 2018

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SummaryHereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue‐specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson–Gilford progeria syndrome (HGPS) and other progeroid syndromes. MicroRNAs are small noncoding RNAs described as powerful regulators of gene expression, mainly by degrading target mRNAs or by inhibiting their translation. In recent years, the role of these small RNAs has become an object of study in laminopathies using in vitro or in vivo murine models as well as cells/tissues of patients. To date, few miRNAs have been reported to exert protective effects in laminopathies, including miR‐9, which prevents progerin accumulation in HGPS neurons. The recent literature has described the potential implication of several other miRNAs in the pathophysiology of laminopathies, mostly by exerting deleterious effects. This review provides an overview of the current knowledge of the functional relevance and molecular insights of miRNAs in laminopathies. Furthermore, we discuss how these discoveries could help to better understand these diseases at the molecular level and could pave the way toward identifying new potential therapeutic targets and strategies based on miRNA modulation.

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A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of thelet-7Small Temporal RNA

Cited by 2,482 publications

References 32 publications

Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum

Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum

FGF‐4 signaling is involved in mir‐206 expression in developing somites of chicken embryos

MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies

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