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  • 1
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    Structure of yeast Argonaute with guide RNA (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-06-23
    Beschreibung: The RNA-induced silencing complex, comprising Argonaute and guide RNA, mediates RNA interference. Here we report the 3.2 A crystal structure of Kluyveromyces polysporus Argonaute (KpAGO) fortuitously complexed with guide RNA originating from small-RNA duplexes autonomously loaded by recombinant KpAGO. Despite their diverse sequences, guide-RNA nucleotides 1-8 are positioned similarly, with sequence-independent contacts to bases, phosphates and 2'-hydroxyl groups pre-organizing the backbone of nucleotides 2-8 in a near-A-form conformation. Compared with prokaryotic Argonautes, KpAGO has numerous surface-exposed insertion segments, with a cluster of conserved insertions repositioning the N domain to enable full propagation of guide-target pairing. Compared with Argonautes in inactive conformations, KpAGO has a hydrogen-bond network that stabilizes an expanded and repositioned loop, which inserts an invariant glutamate into the catalytic pocket. Mutation analyses and analogies to ribonuclease H indicate that insertion of this glutamate finger completes a universally conserved catalytic tetrad, thereby activating Argonaute for RNA cleavage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853139/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853139/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakanishi, Kotaro -- Weinberg, David E -- Bartel, David P -- Patel, Dinshaw J -- AI068776/AI/NIAID NIH HHS/ -- GM61835/GM/NIGMS NIH HHS/ -- R01 AI068776/AI/NIAID NIH HHS/ -- R01 GM061835/GM/NIGMS NIH HHS/ -- R37 GM061835/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jun 20;486(7403):368-74. doi: 10.1038/nature11211.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722195" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Argonaute Proteins/*chemistry/*metabolism ; Base Sequence ; Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Eukaryotic Cells/chemistry/enzymology ; Fungal Proteins/*chemistry/*metabolism ; Kluyveromyces/*chemistry/enzymology ; Models, Molecular ; Molecular Conformation ; Molecular Sequence Data ; RNA, Guide/*chemistry/genetics/*metabolism ; Saccharomycetales/enzymology/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    Maternal and paternal genomes contribute equally to the transcriptome of early plant embryos (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-01-24
    Beschreibung: In animals, maternal gene products deposited into eggs regulate embryonic development before activation of the zygotic genome. In plants, an analogous period of prolonged maternal control over embryogenesis is thought to occur based on some gene-expression studies. However, other gene-expression studies and genetic analyses show that some transcripts must derive from the early zygotic genome, implying that the prevailing model does not fully explain the nature of zygotic genome activation in plants. To determine the maternal, paternal and zygotic contributions to the early embryonic transcriptome, we sequenced the transcripts of hybrid embryos from crosses between two polymorphic inbred lines of Arabidopsis thaliana and used single-nucleotide polymorphisms diagnostic of each parental line to quantify parental contributions. Although some transcripts seemed to be either inherited from primarily one parent or transcribed from imprinted loci, the vast majority of transcripts were produced in near-equal amounts from both maternal and paternal alleles, even during the initial stages of embryogenesis. Results of reporter experiments and analyses of transcripts from genes that are not expressed in sperm and egg indicate early and widespread zygotic transcription. Thus, in contrast to early animal embryogenesis, early plant embryogenesis is mostly under zygotic control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477627/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477627/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nodine, Michael D -- Bartel, David P -- F32 GM084656/GM/NIGMS NIH HHS/ -- GM067031/GM/NIGMS NIH HHS/ -- GM084656/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 22;482(7383):94-7. doi: 10.1038/nature10756.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22266940" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Alleles ; Arabidopsis/*embryology/*genetics ; Crosses, Genetic ; *Gene Expression Profiling ; Gene Expression Regulation, Plant/*genetics ; Genes, Reporter/genetics ; Genome, Plant/*genetics ; Plants, Genetically Modified ; Polymorphism, Single Nucleotide/genetics ; Seeds/*genetics ; Transcriptome/*genetics ; Zygote/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs (2010)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2010-11-19
    Beschreibung: Post-transcriptional gene regulation frequently occurs through elements in mRNA 3' untranslated regions (UTRs). Although crucial roles for 3'UTR-mediated gene regulation have been found in Caenorhabditis elegans, most C. elegans genes have lacked annotated 3'UTRs. Here we describe a high-throughput method for reliable identification of polyadenylated RNA termini, and we apply this method, called poly(A)-position profiling by sequencing (3P-Seq), to determine C. elegans 3'UTRs. Compared to standard methods also recently applied to C. elegans UTRs, 3P-Seq identified 8,580 additional UTRs while excluding thousands of shorter UTR isoforms that do not seem to be authentic. Analysis of this expanded and corrected data set suggested that the high A/U content of C. elegans 3'UTRs facilitated genome compaction, because the elements specifying cleavage and polyadenylation, which are A/U rich, can more readily emerge in A/U-rich regions. Indeed, 30% of the protein-coding genes have mRNAs with alternative, partially overlapping end regions that generate another 10,480 cleavage and polyadenylation sites that had gone largely unnoticed and represent potential evolutionary intermediates of progressive UTR shortening. Moreover, a third of the convergently transcribed genes use palindromic arrangements of bidirectional elements to specify UTRs with convergent overlap, which also contributes to genome compaction by eliminating regions between genes. Although nematode 3'UTRs have median length only one-sixth that of mammalian 3'UTRs, they have twice the density of conserved microRNA sites, in part because additional types of seed-complementary sites are preferentially conserved. These findings reveal the influence of cleavage and polyadenylation on the evolution of genome architecture and provide resources for studying post-transcriptional gene regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057491/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jan, Calvin H -- Friedman, Robin C -- Ruby, J Graham -- Bartel, David P -- GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031-06/GM/NIGMS NIH HHS/ -- R01 GM067031-07/GM/NIGMS NIH HHS/ -- R01 GM067031-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jan 6;469(7328):97-101. doi: 10.1038/nature09616. Epub 2010 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21085120" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 3' Untranslated Regions/*genetics ; AT Rich Sequence/genetics ; Animals ; Caenorhabditis elegans/*genetics ; Conserved Sequence/genetics ; *Evolution, Molecular ; Gene Expression Profiling/methods ; Gene Expression Regulation/*genetics ; Genes, Helminth/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; MicroRNAs/genetics ; Poly A ; Polyadenylation ; RNA, Helminth/genetics ; Regulatory Sequences, Ribonucleic Acid/genetics ; Sequence Alignment ; Sequence Analysis, RNA/methods
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Poly(A)-tail profiling reveals an embryonic switch in translational control (2014)
    Nature Publishing Group (NPG)
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    Publikationsdatum: 2014-01-31
    Beschreibung: Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086860/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subtelny, Alexander O -- Eichhorn, Stephen W -- Chen, Grace R -- Sive, Hazel -- Bartel, David P -- GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 3;508(7494):66-71. doi: 10.1038/nature13007. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA [5]. ; 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4]. ; 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476825" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Arabidopsis/genetics ; Base Sequence ; Cell Line ; Drosophila melanogaster/embryology/genetics ; Gastrulation/genetics ; Gene Expression Regulation, Developmental/*genetics ; Humans ; Liver/metabolism ; Mice ; MicroRNAs/genetics/metabolism ; Models, Genetic ; Plant Leaves/genetics ; Poly A/*analysis/genetics ; Protein Biosynthesis/*genetics ; RNA Stability/genetics ; RNA, Messenger/*genetics/metabolism ; Ribosomes/metabolism ; Sequence Analysis, RNA ; Species Specificity ; Transcription, Genetic ; Xenopus/embryology/genetics ; Yeasts/genetics ; Zebrafish/embryology/genetics ; Zygote/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Compatibility with killer explains the rise of RNAi-deficient fungi (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2011-09-17
    Beschreibung: The RNA interference (RNAi) pathway is found in most eukaryotic lineages but curiously is absent in others, including that of Saccharomyces cerevisiae. We show that reconstituting RNAi in S. cerevisiae causes loss of a beneficial double-stranded RNA virus known as killer virus. Incompatibility between RNAi and killer viruses extends to other fungal species in that RNAi is absent in all species known to possess double-stranded RNA killer viruses, whereas killer viruses are absent in closely related species that retained RNAi. Thus, the advantage imparted by acquiring and retaining killer viruses explains the persistence of RNAi-deficient species during fungal evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790311/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Drinnenberg, Ines A -- Fink, Gerald R -- Bartel, David P -- GM0305010/GM/NIGMS NIH HHS/ -- GM040266/GM/NIGMS NIH HHS/ -- GM061835/GM/NIGMS NIH HHS/ -- R01 GM061835/GM/NIGMS NIH HHS/ -- R37 GM061835/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1592. doi: 10.1126/science.1209575.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21921191" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Biological Evolution ; Fungi/genetics/virology ; Genes, Fungal ; Phylogeny ; *RNA Interference ; RNA Viruses/*physiology ; Saccharomyces cerevisiae/*genetics/physiology/*virology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
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    Mammalian microRNAs predominantly act to decrease target mRNA levels (2010)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2010-08-13
    Beschreibung: MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (〉/=84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990499/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990499/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Huili -- Ingolia, Nicholas T -- Weissman, Jonathan S -- Bartel, David P -- GM080853/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031-06/GM/NIGMS NIH HHS/ -- R01 GM067031-07/GM/NIGMS NIH HHS/ -- R01 GM067031-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 12;466(7308):835-40. doi: 10.1038/nature09267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20703300" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): 3' Untranslated Regions/genetics ; Animals ; Down-Regulation/*genetics ; HeLa Cells ; Humans ; Mammals/genetics ; Mice ; MicroRNAs/*genetics/*metabolism ; Models, Genetic ; Open Reading Frames/genetics ; Protein Biosynthesis/genetics ; RNA Processing, Post-Transcriptional/genetics ; RNA Stability/*genetics ; RNA, Messenger/analysis/*genetics/*metabolism ; Ribosomes/genetics/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    Candida albicans Dicer (CaDcr1) is required for efficient ribosomal and spliceosomal RNA maturation (2011)
    National Academy of Sciences
    Details
    Publikationsdatum: 2011-12-15
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
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  • 8
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    Candida albicans Dicer (CaDcr1) is required for efficient ribosomal and spliceosomal RNA maturation [Genetics] (2012)
    National Academy of Sciences
    Details
    Publikationsdatum: 2012-01-12
    Beschreibung: The generation of mature functional RNAs from nascent transcripts requires the precise and coordinated action of numerous RNAs and proteins. One such protein family, the ribonuclease III (RNase III) endonucleases, includes Rnt1, which functions in fungal ribosome and spliceosome biogenesis, and Dicer, which generates the siRNAs of the RNAi pathway. The recent discovery of small RNAs in Candida albicans led us to investigate the function of C. albicans Dicer (CaDcr1). CaDcr1 is capable of generating siRNAs in vitro and is required for siRNA generation in vivo. In addition, CaDCR1 complements a Dicer knockout in Saccharomyces castellii, restoring RNAi-mediated gene repression. Unexpectedly, deletion of the C. albicans CaDCR1 results in a severe slow-growth phenotype, whereas deletion of another core component of the RNAi pathway (CaAGO1) has little effect on growth, suggesting that CaDCR1 may have an essential function in addition to producing siRNAs. Indeed CaDcr1, the sole functional RNase III enzyme in C. albicans, has additional functions: it is required for cleavage of the 3′ external transcribed spacer from unprocessed pre-rRNA and for processing the 3′ tail of snRNA U4. Our results suggest two models whereby the RNase III enzymes of a fungal ancestor, containing both a canonical Dicer and Rnt1, evolved through a series of gene-duplication and gene-loss events to generate the variety of RNase III enzymes found in modern-day budding yeasts.
    Print ISSN: 0027-8424
    Digitale ISSN: 1091-6490
    Thema: Biologie , Medizin , Allgemeine Naturwissenschaft
    Publiziert von National Academy of Sciences
    Standort Signatur Erwartet Verfügbarkeit
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