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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Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish
TL;DR: Analysis of transcript sequences and ribosome profiling data from human, mouse and zebrafish finds that uORFs are depleted near coding sequences (CDSes) and have initiation contexts that diminish their translation, suggesting that the prevalence of vertebrate UORFs may be explained by their conserved role in repressing CDS translation.
Journal ArticleDOI
Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder
Mohammed Uddin,Kristiina Tammimies,Giovanna Pellecchia,Babak Alipanahi,Pingzhao Hu,Zhuozhi Wang,Dalila Pinto,Lynette Lau,Thomas Nalpathamkalam,Christian R. Marshall,Benjamin J. Blencowe,Brendan J. Frey,Daniele Merico,Ryan K. C. Yuen,Stephen W. Scherer +14 more
TL;DR: The results suggest that brain-expressed exons under purifying selection should be prioritized in genotype-phenotype studies for ASD and related neurodevelopmental conditions.
Journal ArticleDOI
De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder
Shan Dong,Shan Dong,Michael F. Walker,Nicholas Carriero,Michael DiCola,A. Jeremy Willsey,A. Jeremy Willsey,Adam Yongxin Ye,Zainulabedin Waqar,Luis E. Gonzalez,John D. Overton,Stephanie Frahm,John F. Keaney,Nicole A. Teran,Jeanselle Dea,Jeffrey D. Mandell,Vanessa H. Bal,Catherine A.W. Sullivan,Nicholas M. DiLullo,Rehab O. Khalil,Jake Gockley,Zafer Yüksel,Sinem M. Sertel,A. Gulhan Ercan-Sencicek,Abha R. Gupta,Shrikant Mane,Michael Sheldon,Andrew Brooks,Kathryn Roeder,Bernie Devlin,Matthew W. State,Liping Wei,Stephen Sanders,Stephen Sanders +33 more
TL;DR: On the basis of mutation rates in probands versus unaffected siblings, it is concluded that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD.
Journal ArticleDOI
Reactivation of stalled polyribosomes in synaptic plasticity
Tyson E. Graber,Sarah Hébert-Seropian,Arkady Khoutorsky,Alexandre David,Jonathan W. Yewdell,Jean-Claude Lacaille,Wayne S. Sossin +6 more
TL;DR: Evidence is provided for a second mechanism whereby synaptic mRNAs are repressed at elongation/termination awaiting translational reactivation upon appropriate synaptic signals, and metabotropic glutamate receptor activation allows the synthesis of proteins that lead to a functional long-term depression phenotype when translation initiation has been greatly reduced.
Journal ArticleDOI
Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders
Georg Stoll,Olli Pietiläinen,Olli Pietiläinen,Olli Pietiläinen,Bastian Linder,Jaana Suvisaari,Cornelia Brosi,William Hennah,William Hennah,Virpi M. Leppä,Minna Torniainen,Samuli Ripatti,Samuli Ripatti,Sirpa Ala-Mello,Oliver Plöttner,Karola Rehnström,Annamari Tuulio-Henriksson,Teppo Varilo,Teppo Varilo,Jonna Tallila,Kati Kristiansson,Matti Isohanni,Jaakko Kaprio,Jaakko Kaprio,Johan G. Eriksson,Olli T. Raitakari,Olli T. Raitakari,Terho Lehtimäki,Marjo-Riitta Järvelin,Veikko Salomaa,Matthew E. Hurles,Hreinn Stefansson,Leena Peltonen,Patrick F. Sullivan,Tiina Paunio,Tiina Paunio,Tiina Paunio,Jouko Lönnqvist,Jouko Lönnqvist,Mark J. Daly,Mark J. Daly,Utz Fischer,Nelson B. Freimer,Aarno Palotie,Aarno Palotie,Aarno Palotie +45 more
TL;DR: It is found that the enrichment of a rare chromosome 22q11.22 deletion in a recently expanded Northern Finnish sub-isolate enabled the detection of association between TOP3B and both schizophrenia and cognitive impairment and suggests that it is involved in neurodevelopmental disorders.
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