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Resources » Paper

Watabe, Eichi et al. (2019) International Worm Meeting "PES-4 regulates head-muscle-specific alternative splicing of the tropomyosin pre-mRNA."

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  • Comments on Watabe, Eichi et al. (2019) International Worm Meeting "PES-4 regulates head-muscle-specific alternative splicing of the tropomyosin pre-mRNA." (0)

  • Overview

    Status:
    Publication type:
    Meeting_abstract
    WormBase ID:
    WBPaper00058104

    Watabe, Eichi, & KUROYANAGI, Hidehito (2019). PES-4 regulates head-muscle-specific alternative splicing of the tropomyosin pre-mRNA presented in International Worm Meeting. Unpublished information; cite only with author permission.

    In animals, many proteins involved in actin filament organization and functions have multiple isoforms owing to gene duplication and/or alternative pre-mRNA splicing. These isoforms are often expressed in cell-type-specific fashions. However, selection mechanisms and functional consequences of such protein isoforms in specific tissues largely remain to be elucidated. We have recently reported comprehensive analysis of splicing variants for the single tropomyosin gene lev-11 in C. elegans. We found that its novel alternative exon, 7a, is selected only in head muscles, whereas the other muscles and tissues select exon 7b (Mol Biol Cell, 2018; Cytoskeleton, 2018). Here we analyzed alternative splicing regulators of this head-muscle-specific splicing. We crossed dichromatic fluorescence lev-11 exon 7 splicing reporter worms with splicing factor mutants defective in muscle-specific alternative splicing and found that asd-2, a regulator for the let-2 gene and the unc-60 gene, are also involved at least in part in the head-muscle-specific splicing. We further searched recently published single-cell RNA-seq data for RNA-binding proteins enriched in the head muscles and identified pes-4, msi-1 and exc-7 as candidates. msi-1(os1) and exc-7(ok370) did not affect the lev-11 exon 7 splicing reporter. We then knocked out the pes-4 gene in the lev-11 exon 7 splicing reporter worms with CRISPR/Cas9 system and found that the pes-4 mutants completely lost the head-muscle-specific expression of exon 7a, although the homozygotes were arrested at the L1 stage. PES-4 protein has two KH-type RNA-binding domains, an alanine- and glutamine-rich (AQ-rich) region and a conserved C-terminal region. The C-terminal region matches the consensus of proline-tyrosine (PY)-type nuclear localization signal (PY-NLS) and were actually involved in the nuclear localization and function of PES-4. The AQ-rich region is not homologous to any other proteins in the primary sequence, but were essential for the splicing regulation. We are currently elucidating a model for exon 7a selection exclusively in the head muscles.

    Affiliation:
    - Medical Research Institute, Tokyo Med & Dental Univ (TMDU), Bunkyo-ku, Tokyo, JP


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