The ortholog of human ataxin-2 is essential for early embryonic patterning in C. elegans

Tim Rasmus Kiehl, Hiroki Shibata, Stefan M. Pulst

    Research output: Contribution to journalArticlepeer-review

    52 Citations (Scopus)

    Abstract

    Ataxin-2, the gene product of the human spinocerebellar ataxia type 2 (SCA2) gene, is a protein of unknown function. Ataxin-2 interacts with ataxin-2-binding-protein 1 (A2BP1), a member of a novel family of putative RNA-binding proteins. Because the sequences of ataxin-2 and A2BP1 are evolutionarily conserved, we investigated functional aspects and expression pattern in the nematode Caenorhabditis elegans. Human ataxin-2 has 20.1% amino acid identity and 43.9% similarity to its C. elegans ortholog, designated ATX-2, that encodes a predicted 1026 aa protein. One of the worm orthologs of human A2BP1 is the numerator element FOX-1, with an overall 29.8% aa identity. We studied the expression pattern of atx-2 using the endogenous promotor coupled with a GFP expression vector. Atx-2 was widely expressed in the adult worm with strong expression in muscle and nervous tissue. It was also heavily expressed in the embryo. In order to elucidate the function of atx-2 and fox-1, we conducted RNA interference (RNAi) studies. The interfering dsRNA was introduced into larval L4 stage worms of the N2 strain by microinjection or soaking. DsRNA representing the full-length atx-2 gene resulted in arrested embryonic development in the offspring of all 58 microinjected worms. Nomarski imaging showed embryos in different stages of developmental arrest, indicating an essential role of atx-2 for early embryonic development. When fox-1 was targeted by RNAi, there was a marked reduction in the number of eggs per worm. The results presented here underline previous findings about the interaction of human ataxin-2 and A2BP1.

    Original languageEnglish
    Pages (from-to)231-241
    Number of pages11
    JournalJournal of Molecular Neuroscience
    Volume15
    Issue number3
    DOIs
    Publication statusPublished - 2000

    All Science Journal Classification (ASJC) codes

    • Cellular and Molecular Neuroscience

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