Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways
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The findings reveal that despite conservation of the NMD machinery, different mechanisms have evolved to discriminate premature from natural stop codons in metazoa.Abstract:
The nonsense-mediated mRNA decay (NMD) pathway promotes the rapid degradation of mRNAs containing premature stop codons (PTCs) In Caenorhabditis elegans, seven genes (smg1-7) playing an essential role in NMD have been identified Only SMG2-4 (known as UPF1-3) have orthologs in Saccharomyces cerevisiae Here we show that the Drosophila orthologs of UPF1-3, SMG1, SMG5 and SMG6 are required for the degradation of PTC-containing mRNAs, but that there is no SMG7 ortholog in this organism In contrast, orthologs of SMG5-7 are encoded by the human genome and all three are required for NMD In human cells, exon boundaries have been shown to play a critical role in defining PTCs This role is mediated by components of the exon junction complex (EJC) Contrary to expectation, however, we show that the components of the EJC are dispensable for NMD in Drosophila cells Consistently, PTC definition occurs independently of exon boundaries in Drosophila Our findings reveal that despite conservation of the NMD machinery, different mechanisms have evolved to discriminate premature from natural stop codons in metazoaread more
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A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3
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The highways and byways of mRNA decay.
TL;DR: Some of the mechanisms that are used by the cell to mediate and regulate this intriguing process of mRNA decay are discussed.
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The Nonsense-Mediated Decay RNA Surveillance Pathway
TL;DR: Whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC are discussed.
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Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.
TL;DR: It is demonstrated that mammalian telomeres are transcribed into telomeric repeat–containing RNA (TERRA), and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.
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Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics
TL;DR: The acquisition and loss of mRNA-associated proteins accompanies the transition from the pioneer round to subsequent rounds of translation, and from translational competence to substrate for nonsense-mediated mRNA decay.
References
More filters
Journal ArticleDOI
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
Stephen F. Altschul,Thomas L. Madden,Alejandro A. Schäffer,Jinghui Zhang,Zheng Zhang,Webb Miller,David J. Lipman +6 more
TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Journal ArticleDOI
Clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice
TL;DR: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved and modifications are incorporated into a new program, CLUSTAL W, which is freely available.
Journal ArticleDOI
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
TL;DR: ClUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W, providing an integrated system for performing multiple sequence and profile alignments and analysing the results.
Journal ArticleDOI
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
Journal ArticleDOI
The genome sequence of Drosophila melanogaster
Mark Raymond Adams,Susan E. Celniker,Robert A. Holt,Cheryl A. Evans,Jeannine D. Gocayne,Peter Amanatides,Steve Scherer,Peter W. Li,Roger A. Hoskins,R. Galle,Reed A. George,Suzanna E. Lewis,Stephen Richards,Michael Ashburner,Scott Henderson,Granger G. Sutton,Jennifer R. Wortman,Mark Yandell,Qing Zhang,Lin Chen,Rhonda C. Brandon,Yu-Hui Rogers,R. Blazej,Mark Champe,Barret D. Pfeiffer,Kenneth H. Wan,Colleen Doyle,E. G. Baxter,Gregg Helt,Catherine R. Nelson,G. L. Gabor Miklos,Josep F. Abril,A. Agbayani,Huijin An,C. Andrews-Pfannkoch,Danita Baldwin,Richard M. Ballew,Anand Basu,James Baxendale,Leyla Bayraktaroglu,Ellen M. Beasley,Karen Beeson,Panayiotis V. Benos,Benjamin P. Berman,D. Bhandari,Slava Bolshakov,Dana Borkova,Michael R. Botchan,John Bouck,Peter Brokstein,Philippe Brottier,Kenneth C. Burtis,Dana A. Busam,Heather Butler,Edouard Cadieu,I. Chandra,J. Michael Cherry,Simon Cawley,Carl Dahlke,Lionel Davenport,P. Davies,B. de Pablos,Arthur L. Delcher,Zuoming Deng,A. Deslattes Mays,Ian M. Dew,Susanne Dietz,Kristina Dodson,Lisa Doup,Michael Downes,Shannon Dugan-Rocha,B. C. Dunkov,Patrick J. Dunn,K. J. Durbin,Carlos Evangelista,Concepcion Ferraz,Steven Ferriera,Wolfgang Fleischmann,Carl Fosler,Andrei Gabrielian,Neha Garg,William M. Gelbart,Kenneth Glasser,A. Glodek,Fangcheng Gong,J. Harley Gorrell,Zhiping Gu,Ping Guan,Michael Harris,Nomi L. Harris,Damon A. Harvey,Thomas J. Heiman,Judith Hernandez,Jarrett Houck,Damon Hostin,K. Houston,Timothy Howland,Ming-Hui Wei,Chinyere Ibegwam,M. Jalali,Francis Kalush,Gary H. Karpen,Zhaoxi Ke,James A. Kennison,K. A. Ketchum,B. E. Kimmel,Chinnappa D. Kodira,Cheryl L. Kraft,Saul A. Kravitz,David Kulp,Zhongwu Lai,Paul Lasko,Yiding Lei,Alexander Levitsky,Jun Li,Zhenya Li,Yunye Liang,Xiaoying Lin,Xiangjun Liu,B. Mattei,Tina C. McIntosh,Michael P. McLeod,D. McPherson,Gennady V. Merkulov,Natalia Milshina,Clark M. Mobarry,J. Morris,A. Moshrefi,Stephen M. Mount,Mee Moy,Brian Murphy,Lee Murphy,Donna M. Muzny,David L. Nelson,David R. Nelson,Keith Nelson,K. Nixon,Deborah R. Nusskern,Joanne Pacleb,Michael J. Palazzolo,G. S. Pittman,Sue Pan,J. Pollard,Vinita Puri,Martin G. Reese,Knut Reinert,Karin A. Remington,Robert D. C. Saunders,Robert D. C. Saunders,F. Scheeler,H. Shen,B. Christopher Shue,Inga Siden-Kiamos,Michael Simpson,Marian P. Skupski,Thomas J. Smith,Eugene G. Spier,Allan C. Spradling,Mark Stapleton,Renee Strong,E. Sun,Robert Svirskas,C. Tector,Russell Turner,Eli Venter,Aihui Wang,Xianyuan Wang,Zhen Yuan Wang,David A. Wassarman,George M. Weinstock,Jean Weissenbach,Sherita Williams,Trevor Woodage,Kim C. Worley,D. Wu,Shih-Hung Yang,Q. Alison Yao,Jane Ye,R. F. Yeh,Jayshree Zaveri,Ming Zhan,Gefei Zhang,Qi Zhao,Liansheng Zheng,Xiangqun Zheng,Fei Zhong,Wenyan Zhong,X. Zhou,Shiaoping C. Zhu,Xiancan Zhu,Hamilton O. Smith,Richard A. Gibbs,Eugene W. Myers,Gerald M. Rubin,J. Craig Venter +194 more
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.