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Phillip D Zamore

Samuel H Lewis, Kaycee A Quarles, Yujing Yang, Melanie Tanguy, Lise Frézal, Stephen A Smith, Prashant P Sharma, Richard Cordaux, Clément Gilbert, Isabelle Giraud, David H Collins, Phillip D Zamore, Eric A Miska, Peter Sarkies, Francis M Jiggins
In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods...
December 4, 2017: Nature Ecology & Evolution
Phillip D Zamore
No abstract text is available yet for this article.
September 6, 2017: Nature
Cha San Koh, Rohini Madireddy, Timothy J Beane, Phillip D Zamore, Andrei A Korostelev
Eubacterial ribosomal large-subunit methyltransferase H (RlmH) methylates 23S ribosomal RNA pseudouridine 1915 (Ψ1915), which lies near the ribosomal decoding center. The smallest member of the SPOUT superfamily of methyltransferases, RlmH lacks the RNA recognition domain found in larger methyltransferases. The catalytic mechanism of RlmH enzyme is unknown. Here, we describe the structures of RlmH bound to S-adenosyl-methionine (SAM) and the methyltransferase inhibitor sinefungin. Our structural and biochemical studies reveal catalytically essential residues in the dimer-mediated asymmetrical active site...
April 20, 2017: Scientific Reports
Daniel Tianfang Ge, Cindy Tipping, Michael H Brodsky, Phillip D Zamore
Adoption of a streamlined version of the bacterial clustered regular interspersed short palindromic repeat (CRISPR)/Cas9 defense system has accelerated targeted genome engineering. The Streptococcus pyogenes Cas9 protein, directed by a simplified, CRISPR-like single-guide RNA, catalyzes a double-stranded DNA break at a specific genomic site; subsequent repair by end joining can introduce mutagenic insertions or deletions, while repair by homologous recombination using an exogenous DNA template can incorporate new sequences at the target locus...
October 13, 2016: G3: Genes—Genomes—Genetics
Wei Wang, Bo W Han, Cindy Tipping, Daniel Tianfang Ge, Zhao Zhang, Zhiping Weng, Phillip D Zamore
In Drosophila ovarian germ cells, PIWI-interacting RNAs (piRNAs) direct Aubergine and Argonaute3 to cleave transposon transcripts and instruct Piwi to repress transposon transcription, thereby safeguarding the germline genome. Here, we report that RNA cleavage by Argonaute3 initiates production of most Piwi-bound piRNAs. We find that the cardinal function of Argonaute3, whose piRNA guides predominantly correspond to sense transposon sequences, is to produce antisense piRNAs that direct transcriptional silencing by Piwi, rather than to make piRNAs that guide post-transcriptional silencing by Aubergine...
September 3, 2015: Molecular Cell
William E Salomon, Samson M Jolly, Melissa J Moore, Phillip D Zamore, Victor Serebrov
Argonaute proteins repress gene expression and defend against foreign nucleic acids using short RNAs or DNAs to specify the correct target RNA or DNA sequence. We have developed single-molecule methods to analyze target binding and cleavage mediated by the Argonaute:guide complex, RISC. We find that both eukaryotic and prokaryotic Argonaute proteins reshape the fundamental properties of RNA:RNA, RNA:DNA, and DNA:DNA hybridization—a small RNA or DNA bound to Argonaute as a guide no longer follows the well-established rules by which oligonucleotides find, bind, and dissociate from complementary nucleic acid sequences...
July 2, 2015: Cell
Min-Te Chou, Bo W Han, Chiung-Po Hsiao, Phillip D Zamore, Zhiping Weng, Jui-Hung Hung
Small silencing RNAs, including microRNAs, endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), have been shown to play important roles in fine-tuning gene expression, defending virus and controlling transposons. Loss of small silencing RNAs or components in their pathways often leads to severe developmental defects, including lethality and sterility. Recently, non-templated addition of nucleotides to the 3' end, namely tailing, was found to associate with the processing and stability of small silencing RNAs...
September 30, 2015: Nucleic Acids Research
Bo W Han, Wei Wang, Chengjian Li, Zhiping Weng, Phillip D Zamore
PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing transposons. Primary piRNAs, generated from transcripts of genomic transposon "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the subsequent ~26 nt become the first in a series of phased primary piRNAs that bind Piwi, allowing piRNAs to spread beyond the site of RNA cleavage...
May 15, 2015: Science
Christian K Roy, Sara Olson, Brenton R Graveley, Phillip D Zamore, Melissa J Moore
Many RNAs, including pre-mRNAs and long non-coding RNAs, can be thousands of nucleotides long and undergo complex post-transcriptional processing. Multiple sites of alternative splicing within a single gene exponentially increase the number of possible spliced isoforms, with most human genes currently estimated to express at least ten. To understand the mechanisms underlying these complex isoform expression patterns, methods are needed that faithfully maintain long-range exon connectivity information in individual RNA molecules...
2015: ELife
Georgi K Marinov, Jie Wang, Dominik Handler, Barbara J Wold, Zhiping Weng, Gregory J Hannon, Alexei A Aravin, Phillip D Zamore, Julius Brennecke, Katalin Fejes Toth
Huang et al. (2013) recently reported that chromatin immunoprecipitation sequencing (ChIP-seq) reveals the genome-wide sites of occupancy by Piwi, a piRNA-guided Argonaute protein central to transposon silencing in Drosophila. Their study also reported that loss of Piwi causes widespread rewiring of transcriptional patterns, as evidenced by changes in RNA polymerase II occupancy across the genome. Here we reanalyze their data and report that the underlying deep-sequencing dataset does not support the authors' genome-wide conclusions...
March 23, 2015: Developmental Cell
Wei Wang, Mayu Yoshikawa, Bo W Han, Natsuko Izumi, Yukihide Tomari, Zhiping Weng, Phillip D Zamore
PIWI-interacting RNAs (piRNAs) silence transposons in animal germ cells. PIWI proteins bind and amplify piRNAs via the "Ping-Pong" pathway. Because PIWI proteins cleave RNAs between target nucleotides t10 and t11-the nucleotides paired to piRNA guide positions g10 and g11-the first ten nucleotides of piRNAs participating in the Ping-Pong amplification cycle are complementary. Drosophila piRNAs bound to the PIWI protein Aubergine typically begin with uridine (1U), while piRNAs bound to Argonaute3, which are produced by Ping-Pong amplification, often have adenine at position 10 (10A)...
December 4, 2014: Molecular Cell
Bo W Han, Wei Wang, Phillip D Zamore, Zhiping Weng
MOTIVATION: PIWI-interacting RNAs (piRNAs), 23-36 nt small silencing RNAs, repress transposon expression in the metazoan germ line, thereby protecting the genome. Although high-throughput sequencing has made it possible to examine the genome and transcriptome at unprecedented resolution, extracting useful information from gigabytes of sequencing data still requires substantial computational skills. Additionally, researchers may analyze and interpret the same data differently, generating results that are difficult to reconcile...
February 15, 2015: Bioinformatics
Bo W Han, Phillip D Zamore
No abstract text is available yet for this article.
August 18, 2014: Current Biology: CB
Wanzhao Liu, Joanna Chaurette, Edith L Pfister, Lori A Kennington, Kathryn O Chase, Jocelyn Bullock, Jean Paul G Vonsattel, Richard L M Faull, Douglas Macdonald, Marian DiFiglia, Phillip D Zamore, Neil Aronin
BACKGROUND: Huntington's disease is caused by expansion of CAG trinucleotide repeats in the first exon of the huntingtin gene, which is essential for both development and neurogenesis. Huntington's disease is autosomal dominant. The normal allele contains 6 to 35 CAG triplets (average, 18) and the mutant, disease-causing allele contains >36 CAG triplets (average, 42). OBJECTIVE: We examined 279 postmortem brain samples, including 148 HD and 131 non-HD controls...
2013: Journal of Huntington's Disease
Gregory J Babcock, Sowmya Iyer, Heidi L Smith, Yang Wang, Kirk Rowley, Donna M Ambrosino, Phillip D Zamore, Brian G Pierce, Deborah C Molrine, Zhiping Weng
Chronic hepatitis C virus (HCV) infection is the most common cause of end-stage liver disease, often leading to liver transplantation, in which case circulating virions typically infect the transplanted liver within hours and viral concentrations can quickly exceed pre-transplant levels. MBL-HCV1 is a fully human monoclonal antibody recognizing a linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423). The ability of MBL-HCV1 to prevent HCV recurrence after liver transplantation was investigated in a phase 2 randomized clinical trial evaluating six MBL-HCV1-treated subjects and five placebo-treated subjects...
2014: PloS One
Zhao Zhang, Jie Wang, Nadine Schultz, Fan Zhang, Swapnil S Parhad, Shikui Tu, Thom Vreven, Phillip D Zamore, Zhiping Weng, William E Theurkauf
piRNAs guide an adaptive genome defense system that silences transposons during germline development. The Drosophila HP1 homolog Rhino is required for germline piRNA production. We show that Rhino binds specifically to the heterochromatic clusters that produce piRNA precursors, and that binding directly correlates with piRNA production. Rhino colocalizes to germline nuclear foci with Rai1/DXO-related protein Cuff and the DEAD box protein UAP56, which are also required for germline piRNA production. RNA sequencing indicates that most cluster transcripts are not spliced and that rhino, cuff, and uap56 mutations increase expression of spliced cluster transcripts over 100-fold...
June 5, 2014: Cell
Jennifer A Broderick, Phillip D Zamore
In this issue of Molecular Cell, Denzler et al. (2014) report a quantitative study of microRNA function in adult mouse liver, suggesting that the natural abundance of miRNAs and their binding sites generally excludes the previously proposed regulation of miRNAs by competitive endogenous RNAs (ceRNAs).
June 5, 2014: Molecular Cell
Ryuya Fukunaga, Phillip D Zamore
The enzyme Dicer is central to the production of small silencing RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). Like other insects, Drosophila melanogaster uses different Dicers to make siRNAs and miRNAs: Dicer-1 produces miRNAs from pre-miRNAs, whereas Dicer-2 generates siRNAs from long double-stranded RNA (dsRNA). How do the 2 Dicers achieve their substrate specificity? Here, we review recent findings that inorganic phosphate restricts the substrate specificity of Dicer-2 to long dsRNA...
2014: Cell Cycle
Zhao Zhang, Birgit S Koppetsch, Jie Wang, Cindy Tipping, Zhiping Weng, William E Theurkauf, Phillip D Zamore
No abstract text is available yet for this article.
March 18, 2014: EMBO Journal
Yehu Moran, David Fredman, Daniela Praher, Xin Z Li, Liang Meng Wee, Fabian Rentzsch, Phillip D Zamore, Ulrich Technau, Hervé Seitz
In bilaterians, which comprise most of extant animals, microRNAs (miRNAs) regulate the majority of messenger RNAs (mRNAs) via base-pairing of a short sequence (the miRNA "seed") to the target, subsequently promoting translational inhibition and transcript instability. In plants, many miRNAs guide endonucleolytic cleavage of highly complementary targets. Because little is known about miRNA function in nonbilaterian animals, we investigated the repertoire and biological activity of miRNAs in the sea anemone Nematostella vectensis, a representative of Cnidaria, the sister phylum of Bilateria...
April 2014: Genome Research
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