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Eric Miska

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...
October 12, 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...
January 20, 2016: 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...
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
Kristoffer Hylander, Johan Ehrlén, Miska Luoto, Eric Meineri
Microrefugia are sites that support populations of species when their ranges contract during unfavorable climate episodes. Here, we review and discuss two aspects relevant for microrefugia. First, distributions of different species are influenced by different climatic variables. Second, climatic variables differ in the degree of local decoupling from the regional climate. Based on this, we suggest that only species limited by climatic conditions decoupled from the regional climate can benefit from microrefugia...
January 2015: Ambio
Aude S Peden, Patrick Mac, You-Jun Fei, Cecilia Castro, Guoliang Jiang, Kenneth J Murfitt, Eric A Miska, Julian L Griffin, Vadivel Ganapathy, Erik M Jorgensen
No abstract text is available yet for this article.
November 21, 2014: Nature Neuroscience
Aisa Sakaguchi, Peter Sarkies, Matt Simon, Anna-Lisa Doebley, Leonard D Goldstein, Ashley Hedges, Kohta Ikegami, Stacy M Alvares, Liwei Yang, Jeannine R LaRocque, Julie Hall, Eric A Miska, Shawn Ahmed
Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility...
October 14, 2014: Proceedings of the National Academy of Sciences of the United States of America
Raymond H Fetterer, Katarzyna B Miska, Mark C Jenkins, Eric A Wong
The uptake of amino acids is mediated by active transporters located on the basolateral and brush border membranes of intestinal epithelial cells. The current study investigated the expression of amino acid transporters (AAT) and other genes in the intestine of chicks infected with Eimeria maxima. At 7-day postinfection (PI), tissue from each intestinal segment (duodenum, jejunum, and ileum) was taken from birds inoculated with 3 × 10(3) oocysts/bird and processed to recover RNA. Analysis of gene expression was performed using real-time reverse transcription polymerase chain reaction (qRT-PCR)...
October 2014: Parasitology Research
David Brawand, Catherine E Wagner, Yang I Li, Milan Malinsky, Irene Keller, Shaohua Fan, Oleg Simakov, Alvin Y Ng, Zhi Wei Lim, Etienne Bezault, Jason Turner-Maier, Jeremy Johnson, Rosa Alcazar, Hyun Ji Noh, Pamela Russell, Bronwen Aken, Jessica Alföldi, Chris Amemiya, Naoual Azzouzi, Jean-François Baroiller, Frederique Barloy-Hubler, Aaron Berlin, Ryan Bloomquist, Karen L Carleton, Matthew A Conte, Helena D'Cotta, Orly Eshel, Leslie Gaffney, Francis Galibert, Hugo F Gante, Sante Gnerre, Lucie Greuter, Richard Guyon, Natalie S Haddad, Wilfried Haerty, Rayna M Harris, Hans A Hofmann, Thibaut Hourlier, Gideon Hulata, David B Jaffe, Marcia Lara, Alison P Lee, Iain MacCallum, Salome Mwaiko, Masato Nikaido, Hidenori Nishihara, Catherine Ozouf-Costaz, David J Penman, Dariusz Przybylski, Michaelle Rakotomanga, Suzy C P Renn, Filipe J Ribeiro, Micha Ron, Walter Salzburger, Luis Sanchez-Pulido, M Emilia Santos, Steve Searle, Ted Sharpe, Ross Swofford, Frederick J Tan, Louise Williams, Sarah Young, Shuangye Yin, Norihiro Okada, Thomas D Kocher, Eric A Miska, Eric S Lander, Byrappa Venkatesh, Russell D Fernald, Axel Meyer, Chris P Ponting, J Todd Streelman, Kerstin Lindblad-Toh, Ole Seehausen, Federica Di Palma
Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika)...
September 18, 2014: Nature
Eva-Maria Weick, Eric A Miska
Distinguishing self from non-self plays a crucial role in safeguarding the germlines of metazoa from mobile DNA elements. Since their discovery less than a decade ago, Piwi-interacting RNAs (piRNAs) have been shown to repress transposable elements in the germline and, hence, have been at the forefront of research aimed at understanding the mechanisms that maintain germline integrity. More recently, roles for piRNAs in gene regulation have emerged. In this Review, we highlight recent advances made in understanding piRNA function, highlighting the divergent nature of piRNA biogenesis in different organisms, and discussing the mechanisms of piRNA action during transcriptional regulation and in transgenerational epigenetic inheritance...
September 2014: Development
Andrew R Bassett, Asifa Akhtar, Denise P Barlow, Adrian P Bird, Neil Brockdorff, Denis Duboule, Anne Ephrussi, Anne C Ferguson-Smith, Thomas R Gingeras, Wilfried Haerty, Douglas R Higgs, Eric A Miska, Chris P Ponting
Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic...
2014: ELife
Peter Sarkies, Eric A Miska
Small RNAs that function in a non-cell autonomous manner are becoming increasingly recognized as regulatory molecules with the potential to transmit information between cells, organisms and species. In plants and nematodes, small RNA mobility can be genetically dissected to provide information about the nature of the mobile RNA species, their distribution in the organism and inside cells, as well as the cellular machinery required for mobility, including channel proteins and cellular trafficking factors. Mobile RNAs function in antiviral defence, cell signalling and gene expression regulation, and might also mediate transgenerational epigenetic inheritance...
August 2014: Nature Reviews. Molecular Cell Biology
Katarzyna B Miska, Raymond H Fetterer, Eric A Wong
The mRNA expression profile for 10 amino acid transporters, the di-and tri- peptide transporter (PepT1), and aminopeptidase N (APN) during chick embryogenesis was determined. Fertilized eggs were sampled at d 9, 11, 15, 17, 19, and 20 of incubation. Three to 4 embryos were sampled at each time period. At d 9 and 11, the entire intestine was collected due to its undifferentiated appearance. The ceca, duodenum, midgut, and liver were sampled at d 15, 17, 19, and 20. Gene expression was measured using absolute quantitation quantitative reverse-transcription PCR...
September 2014: Poultry Science
Alexandra Sapetschnig, Eric A Miska
The generation of piRNAs from long primary transcripts requires specialized factors that distinguish these precursors from canonical RNA polymerase II transcripts. Mohn et al. and Zhang et al. provide evidence that in Drosophila melanogaster noncanonical transcription coupled with splicing inhibition differentiates piRNA precursors from mRNAs and ensures their correct processing.
June 5, 2014: Cell
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