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Eric Miska

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...
January 2018: Nature Ecology & Evolution
Alicia N McMurchy, Przemyslaw Stempor, Tessa Gaarenstroom, Brian Wysolmerski, Yan Dong, Darya Aussianikava, Alex Appert, Ni Huang, Paulina Kolasinska-Zwierz, Alexandra Sapetschnig, Eric A Miska, Julie Ahringer
No abstract text is available yet for this article.
October 5, 2017: ELife
Mélanie Tanguy, Louise Véron, Przemyslaw Stempor, Julie Ahringer, Peter Sarkies, Eric A Miska
Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode Caenorhabditis elegans, which lacks the interferon system, the major antiviral response so far described is RNA interference (RNAi), but whether additional gene expression responses are employed is not known...
September 5, 2017: MBio
Pieter van Delft, Alper Akay, Sabrina M Huber, Christoph Bueschl, Konrad L M Rudolph, Tomás Di Domenico, Rainer Schuhmacher, Eric A Miska, Shankar Balasubramanian
More than a hundred distinct modified nucleosides have been identified in RNA, but little is known about their distribution across different organisms, their dynamic nature and their response to cellular and environmental stress. Mass-spectrometry-based methods have been at the forefront of identifying and quantifying modified nucleosides. However, they often require synthetic reference standards, which do not exist in the case of many modified nucleosides, and this therefore impedes their analysis. Here we use a metabolic labelling approach to achieve rapid generation of bio-isotopologues of the complete Caenorhabditis elegans transcriptome and its modifications and use them as reference standards to characterise the RNA modification profile in this multicellular organism through an untargeted liquid-chromatography tandem high-resolution mass spectrometry (LC-HRMS) approach...
June 1, 2017: Chembiochem: a European Journal of Chemical Biology
Fabian Braukmann, David Jordan, Eric Miska
Nineteen years after Lisa Timmons and Andy Fire first described RNA transfer from bacteria to C. elegans in an experimental setting 48 the biologic role of this trans-kingdom RNA-based communication remains unknown. Here we summarize our current understanding on the mechanism and potential role of such social RNA.
April 3, 2017: RNA Biology
Alicia N McMurchy, Przemyslaw Stempor, Tessa Gaarenstroom, Brian Wysolmerski, Yan Dong, Darya Aussianikava, Alex Appert, Ni Huang, Paulina Kolasinska-Zwierz, Alexandra Sapetschnig, Eric A Miska, Julie Ahringer
Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways...
March 15, 2017: ELife
Anaïs Bellon, Archana Iyer, Simone Bridi, Flora C Y Lee, Cesaré Ovando-Vázquez, Eloina Corradi, Sara Longhi, Michela Roccuzzo, Stephanie Strohbuecker, Sindhu Naik, Peter Sarkies, Eric Miska, Cei Abreu-Goodger, Christine E Holt, Marie-Laure Baudet
During brain wiring, cue-induced axon behaviors such as directional steering and branching are aided by localized mRNA translation. Different guidance cues elicit translation of subsets of mRNAs that differentially regulate the cytoskeleton, yet little is understood about how specific mRNAs are selected for translation. MicroRNAs (miRNAs) are critical translational regulators that act through a sequence-specific mechanism. Here, we investigate the local role of miRNAs in mRNA-specific translation during pathfinding of Xenopus laevis retinal ganglion cell (RGC) axons...
January 31, 2017: Cell Reports
Sabrina M Huber, Pieter van Delft, Arun Tanpure, Eric A Miska, Shankar Balasubramanian
5-Hydroxymethylcytidine (hm(5)C) was recently identified as a direct metabolite of m(5)C in RNA. We investigated the stability of hm(5)C in human cells using bio-isotopologues and LC-MS/HRMS. This has led to the discovery of a second oxidative metabolite of m(5)C in RNA, namely 2'-O-methyl-5-hydroxymethylcytidine (hm(5)Cm). Subsequent quantitative analysis of total RNA from higher organisms revealed varying levels and TET-independent formation of this new RNA modification.
February 8, 2017: Journal of the American Chemical Society
Adria C LeBoeuf, Patrice Waridel, Colin S Brent, Andre N Gonçalves, Laure Menin, Daniel Ortiz, Oksana Riba-Grognuz, Akiko Koto, Zamira G Soares, Eyal Privman, Eric A Miska, Richard Benton, Laurent Keller
Social insects frequently engage in oral fluid exchange - trophallaxis - between adults, and between adults and larvae. Although trophallaxis is widely considered a food-sharing mechanism, we hypothesized that endogenous components of this fluid might underlie a novel means of chemical communication between colony members. Through protein and small-molecule mass spectrometry and RNA sequencing, we found that trophallactic fluid in the ant Camponotus floridanus contains a set of specific digestion- and non-digestion related proteins, as well as hydrocarbons, microRNAs, and a key developmental regulator, juvenile hormone...
November 29, 2016: ELife
Eric A Miska, Anne C Ferguson-Smith
Heritability has traditionally been thought to be a characteristic feature of the genetic material of an organism-notably, its DNA. However, it is now clear that inheritance not based on DNA sequence exists in multiple organisms, with examples found in microbes, plants, and invertebrate and vertebrate animals. In mammals, the molecular mechanisms have been challenging to elucidate, in part due to difficulties in designing robust models and approaches. Here we review some of the evidence, concepts, and potential mechanisms of non-DNA sequence-based transgenerational inheritance...
October 7, 2016: Science
Helen L Lightfoot, Eric A Miska, Shankar Balasubramanian
The protein Lin28 and microRNA let-7 play critical roles in mammalian development and human disease. Lin28 inhibits let-7 biogenesis through direct interaction with let-7 precursors (pre-let-7). Accumulating evidence in vitro and in vivo suggests this interaction plays a dominant role in embryonic stem cell self-renewal and tumorigenesis. Thus the Lin28-let-7 interaction might be an attractive drug target, if not for the well-known difficulties in targeting protein-RNA interactions with drugs. The identification and development of suitable probe molecules to further elucidate therapeutic potential, as well as mechanistic details of this pathway will be valuable...
November 2, 2016: Organic & Biomolecular Chemistry
Stephanie M Rainey, Julien Martinez, Melanie McFarlane, Punita Juneja, Peter Sarkies, Aleksei Lulla, Esther Schnettler, Margus Varjak, Andres Merits, Eric A Miska, Francis M Jiggins, Alain Kohl
The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus). Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked...
April 2016: PLoS Pathogens
Katharina Gapp, Eric A Miska
Non-genetic inheritance is an evocative topic; in the past few years, the debate around potential inheritance of life-time experiences independent of social factors in mammals has become highly prominent due to increasing evidence for phenotypes in the offspring after paternal environmental exposures. Strikingly, two independent studies published in Science newly implicate a special class of RNA, transfer RNA fragments, in the intergenerational effects of paternal dietary intervention.
April 2016: Cell Research
Amy Cording, Michael Gormally, Peter J Bond, Mark Carrington, Shankar Balasubramanian, Eric A Miska, Beth Thomas
Non-coding RNAs are crucial regulators for a vast array of cellular processes and have been implicated in human disease. These biological processes represent a hitherto untapped resource in our fight against disease. In this work we identify small molecule inhibitors of a non-coding RNA uridylylation pathway. The TUTase family of enzymes is important for modulating non-coding RNA pathways in both human cancer and pathogen systems. We demonstrate that this new class of drug target can be accessed with traditional drug discovery techniques...
May 4, 2017: RNA Biology
Milan Malinsky, Richard J Challis, Alexandra M Tyers, Stephan Schiffels, Yohey Terai, Benjamin P Ngatunga, Eric A Miska, Richard Durbin, Martin J Genner, George F Turner
The genomic causes and effects of divergent ecological selection during speciation are still poorly understood. Here we report the discovery and detailed characterization of early-stage adaptive divergence of two cichlid fish ecomorphs in a small (700 meters in diameter) isolated crater lake in Tanzania. The ecomorphs differ in depth preference, male breeding color, body shape, diet, and trophic morphology. With whole-genome sequences of 146 fish, we identified 98 clearly demarcated genomic "islands" of high differentiation and demonstrated the association of genotypes across these islands with divergent mate preferences...
December 18, 2015: Science
Alper Akay, Peter Sarkies, Eric A Miska
The discovery of RNA interference (RNAi) in C. elegans has had a major impact on scientific research, led to the rapid development of RNAi tools and has inspired RNA-based therapeutics. Astonishingly, nematodes, planaria and many insects take up double-stranded RNA (dsRNA) from their environment to elicit RNAi; the biological function of this mechanism is unclear. Recently, the E. coli OxyS non-coding RNA was shown to regulate gene expression in C. elegans when E. coli is offered as food. This was surprising given that C...
April 15, 2015: Scientific Reports
Katarzyna B Miska, Raymond H Fetterer, Eric A Wong
Amino acid (AA) transporter proteins are responsible for the movement of amino acids in and out of cells. Aminopeptidase cleaves AAs from the N-terminus of polypeptides making them available for transport, while PepT1 is a di- and tripeptide transporter. In the intestine, these proteins are present on the brush border and basolateral membranes of enterocytes, and are essential for the uptake of AAs into enterocytes and their release into circulation. The purpose of this study was to determine the level of transcription of these genes after hatch in 3 regions of the small intestine, the ceca, and liver...
June 2015: Poultry Science
Alexandra Sapetschnig, Peter Sarkies, Nicolas J Lehrbach, Eric A Miska
In the nematode Caenorhabditis elegans, different small RNA-dependent gene silencing mechanisms act in the germline to initiate transgenerational gene silencing. Piwi-interacting RNAs (piRNAs) can initiate transposon and gene silencing by acting upstream of endogenous short interfering RNAs (siRNAs), which engage a nuclear RNA interference (RNAi) pathway to trigger transcriptional gene silencing. Once gene silencing has been established, it can be stably maintained over multiple generations without the requirement of the initial trigger and is also referred to as RNAe or paramutation...
March 2015: PLoS Genetics
Sabrina M Huber, Pieter van Delft, Lee Mendil, Martin Bachman, Katherine Smollett, Finn Werner, Eric A Miska, Shankar Balasubramanian
RNA methylation is emerging as a regulatory RNA modification that could have important roles in the control and coordination of gene transcription and protein translation. Herein, we describe an in vivo isotope-tracing methodology to demonstrate that the ribonucleoside 5-methylcytidine (m(5)C) is subject to oxidative processing in mammals, forming 5-hydroxymethylcytidine (hm(5)C) and 5-formylcytidine (f(5)C). Furthermore, we have identified hm(5)C in total RNA from all three domains of life and in polyA-enriched RNA fractions from mammalian cells...
March 23, 2015: Chembiochem: a European Journal of Chemical Biology
Peter Sarkies, Murray E Selkirk, John T Jones, Vivian Blok, Thomas Boothby, Bob Goldstein, Ben Hanelt, Alex Ardila-Garcia, Naomi M Fast, Phillip M Schiffer, Christopher Kraus, Mark J Taylor, Georgios Koutsovoulos, Mark L Blaxter, Eric A Miska
Small RNA pathways act at the front line of defence against transposable elements across the Eukaryota. In animals, Piwi interacting small RNAs (piRNAs) are a crucial arm of this defence. However, the evolutionary relationships among piRNAs and other small RNA pathways targeting transposable elements are poorly resolved. To address this question we sequenced small RNAs from multiple, diverse nematode species, producing the first phylum-wide analysis of how small RNA pathways evolve. Surprisingly, despite their prominence in Caenorhabditis elegans and closely related nematodes, piRNAs are absent in all other nematode lineages...
February 2015: PLoS Biology
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