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Oxr1 improves pathogenic cellular features of ALS-associated FUS and TDP-43 mutations

15.06.2015 | Mattéa J. Finelli; Kevin X. Liu; Yixing Wu; Peter L. Oliver; Kay E. Davies, Human Molecular Genetics, 2015

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neuron-like cells. Mutations in the RNA- and DNA-binding proteins, fused in sarcoma (FUS) and transactive response DNA-binding protein 43 kDa (TDP-43), are responsible for 5–10% of familial and ...


Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington's disease mice

15.06.2015 | Mayada Achour; Stéphanie Le Gras; Céline Keime; Frédéric Parmentier; François-Xavier Lejeune; Anne-Laurence Boutilli ..., Human Molecular Genetics, 2015

Huntington's disease (HD) is a neurodegenerative disease associated with extensive down-regulation of genes controlling neuronal function, particularly in the striatum. Whether altered epigenetic regulation underlies transcriptional defects in HD is unclear. Integrating RNA-sequencing (RNA-seq) ...


Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decrease glycosylation precursors

01.06.2015 | Bobby G. Ng; Lynne A. Wolfe; Mie Ichikawa; Thomas Markello; Miao He; Cynthia J. Tifft; William A. Gahl; Hudson H. Freeze, Human Molecular Genetics, 2015

In mitochondria, carbamoyl-phosphate synthetase 1 activity produces carbamoyl phosphate for urea synthesis, and deficiency results in hyperammonemia. Cytoplasmic carbamoyl-phosphate synthetase 2, however, is part of a tri-functional enzyme encoded by CAD; no human disease has been attributed to ...


The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes [BIOINFORMATICS]

01.06.2015 | Lorena Pantano; Meritxell Jodar; Mads Bak; Josep Lluís Ballescà; Niels Tommerup; Rafael Oliva; Tanya Vavouri, RNA, 2015

At the end of mammalian sperm development, sperm cells expel most of their cytoplasm and dispose of the majority of their RNA. Yet, hundreds of RNA molecules remain in mature sperm. The biological significance of the vast majority of these molecules is unclear. To better understand the processes ...


Structure-Based Alignment and Consensus Secondary Structures for Three HIV-Related RNA Genomes

20.05.2015 | Christopher A. Lavender et al., PLoS Computational Biology, 2015

by Christopher A. Lavender, Robert J. Gorelick, Kevin M. Weeks HIV and related primate lentiviruses possess single-stranded RNA genomes. Multiple regions of these genomes participate in critical steps in the viral replication cycle, and the functions of many RNA elements are dependent on the ...


Structural and functional analysis of the Rpf2-Rrs1 complex in ribosome biogenesis

19.05.2015 | Nozomi Asano; Koji Kato; Akiyoshi Nakamura; Keisuke Komoda; Isao Tanaka; Min Yao, Nucleic Acids Research, 2015

Proteins Rpf2 and Rrs1 are required for 60S ribosomal subunit maturation. These proteins are necessary for the recruitment of three ribosomal components (5S ribosomal RNA [rRNA], RpL5 and RpL11) to the 90S ribosome precursor and subsequent 27SB pre-rRNA processing. Here we present the crystal ...


The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding

19.05.2015 | Fatemeh Sadeghifar; Stefanie Böhm; Anna Vintermist; Ann-Kristin Östlund Farrants, Nucleic Acids Research, 2015

The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking ...


A serine–arginine-rich (SR) splicing factor modulates alternative splicing of over a thousand genes in Toxoplasma gondii

19.05.2015 | Lee M. Yeoh; Christopher D. Goodman; Nathan E. Hall; Giel G. van Dooren; Geoffrey I. McFadden; Stuart A. Ralph, Nucleic Acids Research, 2015

Single genes are often subject to alternative splicing, which generates alternative mature mRNAs. This phenomenon is widespread in animals, and observed in over 90% of human genes. Recent data suggest it may also be common in Apicomplexa. These parasites have small genomes, and economy of DNA is ...


Implications of macromolecular crowding and reducing conditions for in vitro ribosome construction

19.05.2015 | Brian R. Fritz; Osman K. Jamil; Michael C. Jewett, Nucleic Acids Research, 2015

In vitro construction of Escherichia coli ribosomes could elucidate a deeper understanding of these complex molecular machines and make possible the production of synthetic variants with new functions. Toward this goal, we recently developed an integrated synthesis, assembly and translation ...


CWC22-dependent pre-mRNA splicing and eIF4A3 binding enables global deposition of exon junction complexes

19.05.2015 | Anna-Lena Steckelberg; Janine Altmueller; Christoph Dieterich; Niels H. Gehring, Nucleic Acids Research, 2015

In metazoan cells, spliced mRNAs are marked by the exon junction complex (EJC), a multi-protein complex that serves as a key regulator of post-transcriptional mRNA metabolism. Deposition of EJCs on mRNA is intimately linked to the splicing process. The spliceosomal protein CWC22 directly binds ...


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