REMARKABLE SEQUENCE CONSERVATION OF TRANSCRIPTS ENCODING AMPHIBIAN AND MAMMALIAN HOMOLOGS OF QUAKING, A KH DOMAIN RNA-BINDING PROTEIN

Mutations in the mouse quaking locus can result in two different types of developmental phenotypes: (1) a deficiency of myelin in the centra l nervous system that is accompanied by a characteristic tremor, or (2 ) embryonic lethality around day 9 of gestation. A quaking candidate g ene (qkI) that encodes a KH motif protein has recently been identified . We have isolated and characterized cDNAs encoding the Xenopus quakin g homologue (Xqua) and also assembled an almost complete human quaking sequence from expressed sequence tags. Sequence comparisons show that the amphibian and mammalian quaking transcripts exhibit striking cons ervation, both within the coding region and, unexpectedly, in the 3' U TR. Two Xqua transcripts 5 kb and 5.5 kb in length are differentially expressed in the Xenopus embryo, with the 5 kb transcript being detect ed as early as the gastrula stage of development. Using an in vitro as say, we have demonstrated RNA-binding activity for quaking protein enc oded by the 5 kb transcript. Overall, the high sequence conservation o f quaking sequences suggests an important conserved function in verteb rate development, probably in the regulation of RNA metabolism. (C) 19 97 Elsevier Science B.V.