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Full-Text Articles in Biotechnology
Hits-Clip And Integrative Modeling Define The Rbfox Splicing-Regulatory Network Linked To Brain Development And Autism, Natalie Farny, Sebastien Weyn-Vanhentenryck, Aldo Mele, Qinghong Yan, Shuying Sun, Zuo Zhang, Chenghai Xue, Margaret Herre, Pamela Silver, Michael Zhang, Adrian Krainer, Robert Darnell, Chaolin Zhang
Hits-Clip And Integrative Modeling Define The Rbfox Splicing-Regulatory Network Linked To Brain Development And Autism, Natalie Farny, Sebastien Weyn-Vanhentenryck, Aldo Mele, Qinghong Yan, Shuying Sun, Zuo Zhang, Chenghai Xue, Margaret Herre, Pamela Silver, Michael Zhang, Adrian Krainer, Robert Darnell, Chaolin Zhang
Natalie G. Farny
The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites, combined with additional datasets, define 1,059 direct Rbfox target alternative splicing events. Over half of …
Star Rna-Binding Protein Quaking Suppresses Cancer Via Stabilization Of Specific Mirna, Natalie Farny, An-Jou Chen, Ji-Hye Paik, Hailei Zhang, Sachet Shukla, Richard Mortensen, Jian Hu, Haoqiang Ying, Baoli Hu, Jessica Hurt, Caroline Dong, Yonghong Xiao, Y. Wang, Pamela Silver, Lynda Chin, Shobha Vasudevan, Ronald Depinho
Star Rna-Binding Protein Quaking Suppresses Cancer Via Stabilization Of Specific Mirna, Natalie Farny, An-Jou Chen, Ji-Hye Paik, Hailei Zhang, Sachet Shukla, Richard Mortensen, Jian Hu, Haoqiang Ying, Baoli Hu, Jessica Hurt, Caroline Dong, Yonghong Xiao, Y. Wang, Pamela Silver, Lynda Chin, Shobha Vasudevan, Ronald Depinho
Natalie G. Farny
Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGFβR2 and the TGFβ signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and …
Metazoan Stress Granule Assembly Is Mediated By P-Eif2alpha-Dependent And -Independent Mechanisms, Natalie Farny, Nancy Kedersha, Pamela Silver
Metazoan Stress Granule Assembly Is Mediated By P-Eif2alpha-Dependent And -Independent Mechanisms, Natalie Farny, Nancy Kedersha, Pamela Silver
Natalie G. Farny
Stress granules (SGs) are cytoplasmic bodies wherein translationally silenced mRNAs are recruited for triage in response to environmental stress. We report that Drosophila cells form SGs in response to arsenite and heat shock. Drosophila SGs, like mammalian SGs, are distinct from but adjacent to processing bodies (PBs, sites of mRNA silencing and decay), require polysome disassembly, and are in dynamic equilibrium with polysomes. We further examine the role of the two Drosophila eIF2alpha kinases, PEK and GCN2, in regulating SG formation in response to heat and arsenite stress. While arsenite-induced SGs are dependent upon eIF2alpha phosphorylation, primarily via PEK, heat-induced …
A Conserved Ccch-Type Zinc Finger Protein Regulates Mrna Nuclear Adenylation And Export, Natalie Farny, Jessica Hurt, Robert Obar, Steven Gygi, Pamela Silver, Bo Zhai
A Conserved Ccch-Type Zinc Finger Protein Regulates Mrna Nuclear Adenylation And Export, Natalie Farny, Jessica Hurt, Robert Obar, Steven Gygi, Pamela Silver, Bo Zhai
Natalie G. Farny
Coupling of messenger RNA (mRNA) nuclear export with prior processing steps aids in the fidelity and efficiency of mRNA transport to the cytoplasm. In this study, we show that the processes of export and polyadenylation are coupled via the Drosophila melanogaster CCCH-type zinc finger protein CG6694/dZC3H3 through both physical and functional interactions. We show that depletion of dZC3H3 from S2R+ cells results in transcript hyperadenylation. Using targeted coimmunoprecipitation and liquid chromatography mass spectrometry (MS)/MS techniques, we characterize interactions of known components of the mRNA nuclear export and polyadenylation machineries with dZC3H3. Furthermore, we demonstrate the functional conservation of this factor, …
Definition Of Global And Transcript-Specific Mrna Export Pathways In Metazoans, Natalie Farny, Jessica Hurt, Pamela Silver
Definition Of Global And Transcript-Specific Mrna Export Pathways In Metazoans, Natalie Farny, Jessica Hurt, Pamela Silver
Natalie G. Farny
Eukaryotic gene expression requires export of messenger RNAs (mRNAs) from their site of transcription in the nucleus to the cytoplasm where they are translated. While mRNA export has been studied in yeast, the complexity of gene structure and cellular function in metazoan cells has likely led to increased diversification of these organisms' export pathways. Here we report the results of a genome-wide RNAi screen in which we identify 72 factors required for polyadenylated [poly-(A(+))] mRNA export from the nucleus in Drosophila cells. Using structural and functional conservation analysis of yeast and Drosophila mRNA export factors, we expose the evolutionary divergence …