STRUCTURE AND GENOMIC ORGANIZATION OF THE HUMAN AUF1 GENE - ALTERNATIVE PRE-MESSENGER-RNA SPLICING GENERATES 4 PROTEIN ISOFORMS

The steady-state levels of many mRNAs are determined in part by their turnover rates. Turnover rates, in turn, are usually controlled by pro teins that bind cis-acting sequence elements in mRNAs. One class of ci s-acting instability determinants is composed of A+U-rich elements pre sent in the 3'-UTRs of many labile mRNAs. Many A+U-rich elements are b ound by the AUF1 family of RNA-binding proteins, which may target thes e mRNAs for rapid decay. cDNA cloning and immunoblot analyses suggest that the AUF1 family consists of at least four isoforms. Previous geno mic cloning combined with FISH and Southern analyses of a panel of mon ochromosomal mouse/human or hamster/human somatic cell hybrids localiz ed two AUF1 loci to human 4q21.1-q21.2 and Xq12 (B. Wagner ct al., 199 6, Genomics 34: 219-222). In the present study AUF1 gene organization was examined. The results suggest that the four known AUF1 isoforms ar e generated by alternative pre-mRNA splicing of a transcript encoded b y the chromosome 4 locus. Functionally, this creates isoforms with dif ferent RNA-binding affinities and specificities. Thus, alternative pre -mRNA splicing may serve to create functional versatility within the A UF1 family of proteins. (C) 1998 Academic Press.