RNA-binding Proteins

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Angela N Brooks - One of the best experts on this subject based on the ideXlab platform.

  • regulation of alternative splicing in drosophila by 56 rna binding Proteins
    Genome Research, 2015
    Co-Authors: Angela N Brooks, Michael O Duff, Li Yang, Mohan Bolisetty, Jane M Landolin, Jeremy E Sandler, Benjamin W Booth, Susan E Celniker
    Abstract:

    Alternative splicing is regulated by RNA binding Proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila Proteins, some previously unknown to regulate splicing. Nearly all Proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple Proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP Proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.

James Shorter - One of the best experts on this subject based on the ideXlab platform.

  • the tip of the iceberg rna binding Proteins with prion like domains in neurodegenerative disease
    Brain Research, 2012
    Co-Authors: Oliver D King, Aaron D Gitler, James Shorter
    Abstract:

    Abstract Prions are self-templating protein conformers that are naturally transmitted between individuals and promote phenotypic change. In yeast, prion-encoded phenotypes can be beneficial, neutral or deleterious depending upon genetic background and environmental conditions. A distinctive and portable ‘prion domain’ enriched in asparagine, glutamine, tyrosine and glycine residues unifies the majority of yeast prion Proteins. Deletion of this domain precludes prionogenesis and appending this domain to reporter Proteins can confer prionogenicity. An algorithm designed to detect prion domains has successfully identified 19 domains that can confer prion behavior. Scouring the human genome with this algorithm enriches a select group of RNA-binding Proteins harboring a canonical RNA recognition motif (RRM) and a putative prion domain. Indeed, of 210 human RRM-bearing Proteins, 29 have a putative prion domain, and 12 of these are in the top 60 prion candidates in the entire genome. Startlingly, these RNA-binding prion candidates are inexorably emerging, one by one, in the pathology and genetics of devastating neurodegenerative disorders, including: amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimer's disease and Huntington's disease. For example, FUS and TDP-43, which rank 1st and 10th among RRM-bearing prion candidates, form cytoplasmic inclusions in the degenerating motor neurons of ALS patients and mutations in TDP-43 and FUS cause familial ALS. Recently, perturbed RNA-binding proteostasis of TAF15, which is the 2nd ranked RRM-bearing prion candidate, has been connected with ALS and FTLD-U. We strongly suspect that we have now merely reached the tip of the iceberg. We predict that additional RNA-binding prion candidates identified by our algorithm will soon surface as genetic modifiers or causes of diverse neurodegenerative conditions. Indeed, simple prion-like transfer mechanisms involving the prion domains of RNA-binding Proteins could underlie the classical non-cell-autonomous emanation of neurodegenerative pathology from originating epicenters to neighboring portions of the nervous system. This article is part of a Special Issue entitled RNA-binding Proteins.

Meena Kumari - One of the best experts on this subject based on the ideXlab platform.

  • Guardian of genetic messenger-RNA-binding Proteins
    Biomolecules, 2016
    Co-Authors: Antje Anji, Meena Kumari
    Abstract:

    RNA in cells is always associated with RNA-binding Proteins that regulate all aspects of RNA metabolism including RNA splicing, export from the nucleus, RNA localization, mRNA turn-over as well as translation. Given their diverse functions, cells express a variety of RNA-binding Proteins, which play important roles in the pathologies of a number of diseases. In this review we focus on the effect of alcohol on different RNA-binding Proteins and their possible contribution to alcohol-related disorders, and discuss the role of these Proteins in the development of neurological diseases and cancer. We further discuss the conventional methods and newer techniques that are employed to identify RNA-binding Proteins.

Naoyuki Kataoka - One of the best experts on this subject based on the ideXlab platform.

  • MESSENGER-RNA-binding Proteins AND THE MESSAGES THEY CARRY
    Nature Reviews Molecular Cell Biology, 2002
    Co-Authors: Gideon Dreyfuss, V. Narry Kim, Naoyuki Kataoka
    Abstract:

    From sites of transcription in the nucleus to the outreaches of the cytoplasm, messenger RNAs are associated with RNA-binding Proteins. These Proteins influence pre-mRNA processing as well as the transport, localization, translation and stability of mRNAs. Recent discoveries have shown that one group of these Proteins marks exon exon junctions and has a role in mRNA export. These Proteins communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation.

Gideon Dreyfuss - One of the best experts on this subject based on the ideXlab platform.

  • Isolation and characterization of RNA-binding Proteins from Drosophila melanogaster.
    Methods in Cell Biology, 2008
    Co-Authors: Michael J. Matunis, Erika Matunis, Gideon Dreyfuss
    Abstract:

    Publisher Summary This chapter discusses biochemical approaches that can be used to isolate, purify, and characterize RNA-binding Proteins in Drosophila melanogaster . The same procedures are also applicable to the isolation of Proteins from other tissues, other organisms, and from cultured cells. The most common affinity chromatography procedure used for the isolation of RNA-binding Proteins from D. melanogaster is single stranded (ssDNA)-cellulose chromatography. Overall, purification can be accomplished rapidly and on a large scale. It does not depend on the integrity of RNA and does not require protein denaturing conditions. Individual RNA-binding Proteins can be separated from one another on the same column, owing to their different affinities for ssDNA. This procedure is used to isolate and characterize heterogeneous nuclear ribonucleoprotein (hnRNP) Proteins from human HeLa cells. Proteins not related to RNA metabolism may also bind to ssDNA-cellulose and conversely, not all RNAbinding Proteins will necessarily bind to ssDNA. Therefore, binding to ssDNA is not by itself an absolute diagnostic criterion for RNA-binding Proteins, and the identification of genuine RNA-binding Proteins must be supported by complimentary data.

  • MESSENGER-RNA-binding Proteins AND THE MESSAGES THEY CARRY
    Nature Reviews Molecular Cell Biology, 2002
    Co-Authors: Gideon Dreyfuss, V. Narry Kim, Naoyuki Kataoka
    Abstract:

    From sites of transcription in the nucleus to the outreaches of the cytoplasm, messenger RNAs are associated with RNA-binding Proteins. These Proteins influence pre-mRNA processing as well as the transport, localization, translation and stability of mRNAs. Recent discoveries have shown that one group of these Proteins marks exon exon junctions and has a role in mRNA export. These Proteins communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation.

  • RNA-binding Proteins as regulators of gene expression
    Current Opinion in Genetics & Development, 1997
    Co-Authors: Haruhiko Siomi, Gideon Dreyfuss
    Abstract:

    Abstract A plethora of post-transcriptional mechanisms are involved in essential steps in the pathway of genetic information expression in eukaryotes. These processes are specified by cis -acting signals on RNAs and are mediated by specific trans -acting factors, including RNA-binding Proteins and small complementary RNAs. Recent information has begun to define the molecular mechanisms by which RNA-binding Proteins recognize specific RNA sequences and influence the processing and function of RNA molecules.

  • Conserved structures and diversity of functions of RNA-binding Proteins.
    Science, 1994
    Co-Authors: Christopher G. Burd, Gideon Dreyfuss
    Abstract:

    In eukaryotic cells, a multitude of RNA-binding Proteins play key roles in the posttranscriptional regulation of gene expression. Characterization of these Proteins has led to the identification of several RNA-binding motifs, and recent experiments have begun to illustrate how several of them bind RNA. The significance of these interactions is reflected in the recent discoveries that several human and other vertebrate genetic disorders are caused by aberrant expression of RNA-binding Proteins. The major RNA-binding motifs are described and examples of how they may function are given.