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  • 1
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    Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-10-03
    Description: In bilaterian animals, such as humans, flies and worms, hundreds of microRNAs (miRNAs), some conserved throughout bilaterian evolution, collectively regulate a substantial fraction of the transcriptome. In addition to miRNAs, other bilaterian small RNAs, known as Piwi-interacting RNAs (piRNAs), protect the genome from transposons. Here we identify small RNAs from animal phyla that diverged before the emergence of the Bilateria. The cnidarian Nematostella vectensis (starlet sea anemone), a close relative to the Bilateria, possesses an extensive repertoire of miRNA genes, two classes of piRNAs and a complement of proteins specific to small-RNA biology comparable to that of humans. The poriferan Amphimedon queenslandica (sponge), one of the simplest animals and a distant relative of the Bilateria, also possesses miRNAs, both classes of piRNAs and a full complement of the small-RNA machinery. Animal miRNA evolution seems to have been relatively dynamic, with precursor sizes and mature miRNA sequences differing greatly between poriferans, cnidarians and bilaterians. Nonetheless, miRNAs and piRNAs have been available as classes of riboregulators to shape gene expression throughout the evolution and radiation of animal phyla.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837422/" 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/PMC3837422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimson, Andrew -- Srivastava, Mansi -- Fahey, Bryony -- Woodcroft, Ben J -- Chiang, H Rosaria -- King, Nicole -- Degnan, Bernard M -- Rokhsar, Daniel S -- Bartel, David P -- R01 GM067031/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 30;455(7217):1193-7. doi: 10.1038/nature07415. Epub 2008 Oct 1.〈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/18830242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Gene Expression Regulation ; Humans ; MicroRNAs/*genetics ; Phylogeny ; RNA, Small Interfering/*genetics ; Sea Anemones/*genetics ; Sequence Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-05-09
    Description: In contrast to microRNAs and Piwi-associated RNAs, short interfering RNAs (siRNAs) are seemingly dispensable for host-directed gene regulation in Drosophila. This notion is based on the fact that mutants lacking the core siRNA-generating enzyme Dicer-2 or the predominant siRNA effector Argonaute 2 are viable, fertile and of relatively normal morphology. Moreover, endogenous Drosophila siRNAs have not yet been identified. Here we report that siRNAs derived from long hairpin RNA genes (hpRNAs) programme Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors (Dicer-2, Hen1 (known as CG12367) and Argonaute 2) with a canonical microRNA factor (Loquacious) to generate approximately 21-nucleotide siRNAs. These novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biological usage of endogenous RNA interference in Drosophila.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735555/" 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/PMC2735555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okamura, Katsutomo -- Chung, Wei-Jen -- Ruby, J Graham -- Guo, Huili -- Bartel, David P -- Lai, Eric C -- GM067031/GM/NIGMS NIH HHS/ -- GM083300/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031-01/GM/NIGMS NIH HHS/ -- R01 GM083300/GM/NIGMS NIH HHS/ -- R01 GM083300-01/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jun 5;453(7196):803-6. doi: 10.1038/nature07015. Epub 2008 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sloan-Kettering Institute, Department of Developmental Biology, 521 Rockefeller Research Laboratories, 1275 York Avenue, Box 252, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18463630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/enzymology/*genetics/metabolism ; Methyltransferases/metabolism ; MicroRNAs/biosynthesis/genetics/metabolism ; *Nucleic Acid Conformation ; RNA Helicases/genetics/metabolism ; *RNA Interference ; RNA, Double-Stranded/chemistry/genetics/*metabolism ; RNA, Small Interfering/biosynthesis/genetics/*metabolism ; RNA-Binding Proteins/genetics/metabolism ; RNA-Induced Silencing Complex/genetics/metabolism ; Ribonuclease III
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  • 3
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    The impact of microRNAs on protein output (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-08-01
    Description: MicroRNAs are endogenous approximately 23-nucleotide RNAs that can pair to sites in the messenger RNAs of protein-coding genes to downregulate the expression from these messages. MicroRNAs are known to influence the evolution and stability of many mRNAs, but their global impact on protein output had not been examined. Here we use quantitative mass spectrometry to measure the response of thousands of proteins after introducing microRNAs into cultured cells and after deleting mir-223 in mouse neutrophils. The identities of the responsive proteins indicate that targeting is primarily through seed-matched sites located within favourable predicted contexts in 3' untranslated regions. Hundreds of genes were directly repressed, albeit each to a modest degree, by individual microRNAs. Although some targets were repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA destabilization, and, for the more highly repressed targets, mRNA destabilization usually comprised the major component of repression. The impact of microRNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine-scale adjustments to protein output.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745094/" 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/PMC2745094/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baek, Daehyun -- Villen, Judit -- Shin, Chanseok -- Camargo, Fernando D -- Gygi, Steven P -- Bartel, David P -- R01 GM067031/GM/NIGMS NIH HHS/ -- R01 HG003456/HG/NHGRI NIH HHS/ -- R01 HG003456-04A1/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Sep 4;455(7209):64-71. doi: 10.1038/nature07242. Epub 2008 Jul 30.〈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/18668037" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; HeLa Cells ; Humans ; Isotope Labeling ; Male ; Mice ; MicroRNAs/*genetics/*metabolism ; Neutrophils/metabolism ; Oligonucleotide Array Sequence Analysis ; *Protein Biosynthesis ; Proteomics ; Transfection
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  • 4
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    Structure of yeast Argonaute with guide RNA (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-23
    Description: 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〉
    Keywords: 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
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  • 5
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    Maternal and paternal genomes contribute equally to the transcriptome of early plant embryos (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-01-24
    Description: 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〉
    Keywords: 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
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  • 6
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    Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-11-19
    Description: 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〉
    Keywords: 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
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  • 7
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    Poly(A)-tail profiling reveals an embryonic switch in translational control (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-01-31
    Description: 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〉
    Keywords: 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
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  • 8
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    Mammalian microRNAs predominantly act to decrease target mRNA levels (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-13
    Description: 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〉
    Keywords: 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
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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