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Mutations in the mouse indicate that  quaking  gene function is essential for both embryogenesis and for development of the nervous system. Recent isolation of the mouse  quaking  gene identified a putative RNA-binding protein containing a single KH domain. We have previously isolated the  Xenopus  homolog of  quaking, Xqua,  and shown that the sequence is highly conserved through evolution. Here, we report experimental data on the biochemical function of the quaking protein and its role during development. We demonstrate that the quaking protein expressed during early embryogenesis, pXqua 357 , can bind RNA in vitro, and we have mapped the regions of the protein that are essential for RNA binding. We present evidence that pXqua can form homodimers and that dimerization may be required for RNA binding. Oocyte injection experiments show that pXqua 357  is located in both the nucleus and cytoplasm. In the  Xenopus  embryo,  Xqua  is first expressed during gastrulation in the organizer region and its derivative, the notochord. In later stage embryos,  Xqua  is expressed in a number of mesodermal and neural tissues. We demonstrate that disruption of normal  Xqua  function, by overexpression of a dominant inhibitory form of the protein, blocks notochord differentiation.  Xqua  function appears to be required for the accumulation of important mRNAs such as  Xnot, Xbra,  and gsc.  These results indicate an essential role for the quaking RNA-binding protein during early vertebrate embryogenesis.

The KH domain protein encoded by quaking functions as a dimer and is essential for notochord development inXenopus embryos