FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism
Jennifer C. Darnell,Sarah J. Van Driesche,Chaolin Zhang,Ka Ying Sharon Hung,Aldo Mele,Claire E. Fraser,Elizabeth F. Stone,Cynthia Chen,John J. Fak,Sung Wook Chi,Donny D. Licatalosi,Joel D. Richter,Robert B. Darnell,Robert B. Darnell +13 more
TLDR
A brain polyribosome-programmed translation system is developed, revealing that FMRP reversibly stalls ribosomes specifically on its target mRNAs and suggests multiple targets for clinical intervention in FXS and ASD.About:
This article is published in Cell.The article was published on 2011-07-22 and is currently open access. It has received 1861 citations till now. The article focuses on the topics: FMR1 & RNA-binding protein.read more
Citations
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Journal ArticleDOI
Synaptic, transcriptional and chromatin genes disrupted in autism
Silvia De Rubeis,Xin-Xin He,Arthur P. Goldberg,Christopher S. Poultney,Kaitlin E. Samocha,A. Ercument Cicek,Yan Kou,Li Liu,Menachem Fromer,Menachem Fromer,R. Susan Walker,Tarjinder Singh,Lambertus Klei,Jack A. Kosmicki,Shih-Chen Fu,Branko Aleksic,Monica Biscaldi,Patrick Bolton,Jessica M. Brownfeld,Jinlu Cai,Nicholas G. Campbell,Angel Carracedo,Angel Carracedo,Maria H. Chahrour,Andreas G. Chiocchetti,Hilary Coon,Emily L. Crawford,Lucy Crooks,Sarah Curran,Geraldine Dawson,Eftichia Duketis,Bridget A. Fernandez,Louise Gallagher,Evan T. Geller,Stephen J. Guter,R. Sean Hill,R. Sean Hill,Iuliana Ionita-Laza,Patricia Jiménez González,Helena Kilpinen,Sabine M. Klauck,Alexander Kolevzon,Irene Lee,Jing Lei,Terho Lehtimäki,Chiao-Feng Lin,Avi Ma'ayan,Christian R. Marshall,Alison L. McInnes,Benjamin M. Neale,Michael John Owen,Norio Ozaki,Mara Parellada,Jeremy R. Parr,Shaun Purcell,Kaija Puura,Deepthi Rajagopalan,Karola Rehnström,Abraham Reichenberg,Aniko Sabo,Michael Sachse,Stephen Sanders,Chad M. Schafer,Martin Schulte-Rüther,David Skuse,David Skuse,Christine Stevens,Peter Szatmari,Kristiina Tammimies,Otto Valladares,Annette Voran,Li-San Wang,Lauren A. Weiss,A. Jeremy Willsey,Timothy W. Yu,Timothy W. Yu,Ryan K. C. Yuen,Edwin H. Cook,Christine M. Freitag,Michael Gill,Christina M. Hultman,Thomas Lehner,Aarno Palotie,Aarno Palotie,Aarno Palotie,Gerard D. Schellenberg,Pamela Sklar,Matthew W. State,James S. Sutcliffe,Christopher A. Walsh,Christopher A. Walsh,Stephen W. Scherer,Michael E. Zwick,Jeffrey C. Barrett,David J. Cutler,Kathryn Roeder,Bernie Devlin,Mark J. Daly,Mark J. Daly,Joseph D. Buxbaum +99 more
TL;DR: Using exome sequencing, it is shown that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate of < 0.05, plus a set of 107 genes strongly enriched for those likely to affect risk (FDR < 0.30).
Journal ArticleDOI
The contribution of de novo coding mutations to autism spectrum disorder
Ivan Iossifov,Brian J. O'Roak,Stephen Sanders,Stephen Sanders,Michael Ronemus,Niklas Krumm,Dan Levy,Holly A.F. Stessman,Kali Witherspoon,Laura Vives,Karynne E. Patterson,Joshua D. Smith,Bryan W. Paeper,Deborah A. Nickerson,Jeanselle Dea,Shan Dong,Shan Dong,Luis E. Gonzalez,Jeffrey D. Mandell,Shrikant Mane,Michael T. Murtha,Catherine A.W. Sullivan,Michael F. Walker,Zainulabedin Waqar,Liping Wei,A. Jeremy Willsey,A. Jeremy Willsey,Boris Yamrom,Yoon-ha Lee,Ewa A. Grabowska,Ertugrul Dalkic,Ertugrul Dalkic,Zihua Wang,Steven Marks,Peter Andrews,Anthony Leotta,Jude Kendall,Inessa Hakker,Julie Rosenbaum,Beicong Ma,Linda Rodgers,Jennifer Troge,Giuseppe Narzisi,Seungtai Yoon,Michael C. Schatz,Kenny Ye,W. Richard McCombie,Jay Shendure,Evan E. Eichler,Evan E. Eichler,Matthew W. State,Matthew W. State,Michael Wigler +52 more
TL;DR: It is estimated that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation.
Journal ArticleDOI
Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes
TL;DR: A suite of techniques, based on ribosome profiling, are presented to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation, revealing an unanticipated complexity to mammalian proteomes.
Journal ArticleDOI
De novo mutations in schizophrenia implicate synaptic networks
Menachem Fromer,Andrew Pocklington,David J. Kavanagh,Hywel Williams,Sarah Dwyer,Padhraig Gormley,Lyudmila Georgieva,Elliott Rees,Priit Palta,Douglas M. Ruderfer,Noa Carrera,Isla Humphreys,Jessica S. Johnson,Panos Roussos,Douglas Barker,Eric Banks,Vihra Milanova,Seth G. N. Grant,Eilis Hannon,Samuel A. Rose,Kimberly Chambert,Milind Mahajan,Edward M. Scolnick,Jennifer L. Moran,George Kirov,Aarno Palotie,Steven A. McCarroll,Peter Holmans,Pamela Sklar,Michael John Owen,Shaun Purcell,Michael Conlon O'Donovan +31 more
TL;DR: Genes affected by mutations in schizophrenia overlap those mutated in autism and intellectual disability, as do mutation-enriched synaptic pathways, and pathophysiology shared with other neurodevelopmental disorders.
Journal ArticleDOI
De Novo Gene Disruptions in Children on the Autistic Spectrum
Ivan Iossifov,Michael Ronemus,Dan Levy,Zihua Wang,Inessa Hakker,Julie Rosenbaum,Boris Yamrom,Yoon-ha Lee,Giuseppe Narzisi,Anthony Leotta,Jude Kendall,Ewa A. Grabowska,Beicong Ma,Steven Marks,Linda Rodgers,Asya Stepansky,Jennifer Troge,Peter Andrews,Mitchell A. Bekritsky,Kith Pradhan,Elena Ghiban,Melissa Kramer,Jennifer Parla,Ryan Demeter,Lucinda Fulton,Robert S. Fulton,Vincent Magrini,Kenny Ye,Jennifer C. Darnell,Robert B. Darnell,Robert B. Darnell,Elaine R. Mardis,Richard K. Wilson,Michael C. Schatz,Richard W. McCombie,Michael Wigler +35 more
TL;DR: Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveals de novo small indels and point substitutions, which suggest FMRP-associated genes are especially dosage-sensitive targets of cognitive disorders.
References
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(127) Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: Role of mGluR1/5 and mTOR
TL;DR: Experiments show that translation regulation via FMRP and mTOR is an important feature of nociceptive plasticity, and support the hypothesis that the persistence of self-injurious behavior observed in fragile X mental retardation patients could be related to deficits in nocICEptive sensitization.
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Michael D. R. Croning,Michael C. Marshall,Peter McLaren,J. Douglas Armstrong,Seth G. N. Grant +4 more
TL;DR: The synapse proteome datasets that G2Cdb provides offer a basis for future work in synapse biology and provide useful information on brain diseases and investigators can rapidly query whether a gene or protein is found in brain-signalling complex, has a phenotype in rodent models or whether mutations are associated with a human disease.
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Translational control of ornithine aminotransferase. Modulation by initiation factor eIF-4E.
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TL;DR: Current research focuses on mechanisms whereby mRNAs are transported in a translationally repressed state from soma to distal process and are activated at synaptic sites in response to synaptic signals.
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