Journal ArticleDOI
CLIP identifies Nova-regulated RNA networks in the brain.
Jernej Ule,Kirk B. Jensen,Kirk B. Jensen,Matteo Ruggiu,Matteo Ruggiu,Aldo Mele,Aldo Mele,Aljaž Ule,Robert B. Darnell,Robert B. Darnell +9 more
TLDR
CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA.Abstract:
Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA), an autoimmune neurologic disease characterized by abnormal motor inhibition Nova proteins regulate neuronal pre-messenger RNA splicing by directly binding to RNA To identify Nova RNA targets, we developed a method to purify protein-RNA complexes from mouse brain with the use of ultraviolet cross-linking and immunoprecipitation (CLIP)Thirty-four transcripts were identified multiple times by Nova CLIPThree-quarters of these encode proteins that function at the neuronal synapse, and one-third are involved in neuronal inhibitionSplicing targets confirmed in Nova-/- mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory gamma-aminobutyric acid and glycine receptors, two previously identified Nova splicing targetsThus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMAread more
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Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP
Markus Hafner,Markus Landthaler,Lukas Burger,Mohsen Khorshid,Jean Hausser,Philipp Berninger,Andrea Rothballer,Manuel Ascano,Anna-Carina Jungkamp,Mathias Munschauer,Alexander Ulrich,Greg S. Wardle,Scott Dewell,Mihaela Zavolan,Thomas Tuschl +14 more
TL;DR: This study developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs and revealed that these factors bind thousands of sites containing defined sequence motifs and have distinct preferences for exonic versus intronic or coding versus untranslated transcript regions.
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
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
TL;DR: 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.
Journal ArticleDOI
lincRNAs act in the circuitry controlling pluripotency and differentiation
Mitchell Guttman,Julie Donaghey,Bryce W. Carey,Manuel Garber,Jennifer K. Grenier,Glen Munson,Geneva Young,Anne Bergstrom Lucas,Robert A. Ach,Laurakay Bruhn,Xiaoping Yang,Ido Amit,Alexander Meissner,Alexander Meissner,Aviv Regev,Aviv Regev,John L. Rinn,John L. Rinn,David E. Root,Eric S. Lander,Eric S. Lander,Eric S. Lander +21 more
TL;DR: It is shown that Knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators.
Journal ArticleDOI
Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins
Alfredo Castello,Bernd Fischer,Katrin Eichelbaum,Rastislav Horos,Benedikt M. Beckmann,Claudia Strein,Norman E. Davey,David T. Humphreys,Thomas Preiss,Thomas Preiss,Lars M. Steinmetz,Jeroen Krijgsveld,Matthias W. Hentze,Matthias W. Hentze +13 more
TL;DR: Unexpectedly, it is found that many proteins of the HeLa mRNA interactome are highly intrinsically disordered and enriched in short repetitive amino acid motifs.
References
More filters
Journal ArticleDOI
Mechanisms of Alternative Pre-Messenger RNA Splicing
TL;DR: This review describes what is currently known of the molecular mechanisms that control changes in splice site choice and starts with the best-characterized systems from the Drosophila sex determination pathway, and then describes the regulators of other systems about whose mechanisms there is some data.
Journal ArticleDOI
Selective interaction of JNK protein kinase isoforms with transcription factors.
Shashi Gupta,Tamera Barrett,Alan J. Whitmarsh,Julie Cavanagh,Hayla Karen Sluss,Benoit Dérijard,Roger J. Davis +6 more
TL;DR: Comparison of the binding activity of the JNK isoforms demonstrated that the J NK proteins differ in their interaction with ATF2, Elk‐1 and Jun transcription factors, suggesting that individual members of theJNK group may selectively target specific transcription factors in vivo.
Journal ArticleDOI
Microarray Identification of FMRP-Associated Brain mRNAs and Altered mRNA Translational Profiles in Fragile X Syndrome
Victoria Brown,Victoria Brown,Peng Jin,Peng Jin,Stephanie Ceman,Stephanie Ceman,Jennifer C. Darnell,William T. O'Donnell,William T. O'Donnell,Scott A. Tenenbaum,Xiaokui Jin,Yue Feng,Keith D. Wilkinson,Jack D. Keene,Robert B. Darnell,Stephen T. Warren,Stephen T. Warren +16 more
TL;DR: It is concluded that translational dysregulation of mRNAs normally associated with FMRP may be the proximal cause of fragile X syndrome, and candidate genes relevant to this phenotype are identified.
Journal ArticleDOI
Deleted in Colorectal Cancer (DCC) Encodes a Netrin Receptor
Kazuko Keino-Masu,Kazuko Keino-Masu,Masayuki Masu,Lindsay Hinck,E.David Leonardo,Shirley S.-Y Chan,Joseph G. Culotti,Marc Tessier-Lavigne +7 more
TL;DR: Results indicate that DCC is a receptor or a component of a receptor that mediates the effects of netrin-1 on commissural axons, and they complement genetic evidence for interactions between DCC and netrin homologs in C. elegans and Drosophila.
Journal ArticleDOI
Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus
Michael R. Lerner,Joan A. Steitz +1 more
TL;DR: It is argued that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000.