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Resources » Paper

Gonzales, Patrick K. (2013) International Worm Meeting "Transcriptome analysis of ALS-associated Mutants fust-1 and tdp-1."

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  • Comments on Gonzales, Patrick K. (2013) International Worm Meeting "Transcriptome analysis of ALS-associated Mutants fust-1 and tdp-1." (0)

  • Overview

    Status:
    Publication type:
    Meeting_abstract
    WormBase ID:
    WBPaper00043234

    Gonzales, Patrick K. (2013). Transcriptome analysis of ALS-associated Mutants fust-1 and tdp-1 presented in International Worm Meeting. Unpublished information; cite only with author permission.

    ALS is an adult-onset neurodegenerative disorder characterized by premature degeneration of upper and lower motor neurons eventually leading to fatal paralysis. Approximately 10% of disease instances are familial, with several dominant mutations identified. TDP43 (TAR DNA-binding protein 43) and FUS (fused in sarcoma), are two RNA binding proteins whose mutations are present in a subset of familial ALS cases. Interestingly, the two proteins share structural and functional similarities. Both contain RNA recognition motifs, have glycine rich regions, and both are associated with multiple steps of RNA processing including transcription, RNA splicing, RNA transport and translation. ALS-associated mutations in TDP-43 and FUS suggest defects in RNA processing could result in ALS. In order to understand which RNA processing defects are central to the disease process, it is important to determine which RNA transcripts depend on both proteins for correct abundance and processing. To answer this question we analyzed the transcriptome of strains deleted for the C. elegans homologs of TDP-43 and Fus, tdp-1 and fust-1. Deletion alleles, tdp-1(ok803) and fust-1(tm4439), are viable and display only mild phenotypes. Previous high throughput sequencing analysis from our lab showed that tdp-1(ok803) preferentially binds transcripts with potential dsRNA structure and limits this structure, particularly within introns. In this study we asked if fust-1 mutants have a similar expression profile as the tdp-1 mutant. We used high throughput sequencing of N2, tdp-1(ok803), and fust-1(tm4439) to characterize altered transcripts in both mutants from total RNA and from RNA captured using a dsRNA specific antibody (J2). The results of this comparison are reported.

    Affiliation:
    - Integrative Physiology, University of Colorado Boulder, Boulder, CO.


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