CHARACTERIZATION OF CDNAS ENCODING THE MURINE A-RICH RNA-BINDING PROTEIN AUF1(U)

A + U-rich elements (ARE) serve to control the degradation of some pro to-oncogene and lymphokine mRNAs. The protein, AUF1, which consists of two polypeptides of 37 and 40 kDa (p37 and p40, respectively) when pu rified from cytosol, has been implicated in ARE-directed mRNA turnover due to its binding to ARE. Molecular cloning of a cDNA (p37(AUF1)) co rresponding to human p37 predicted a polypeptide containing two non-id entical RNA recognition motifs (RRM) and a C-terminal Gln-rich domain [Zhang et al. Mol. Cell. Biol. 13 (1993) 7652-7665]. Two cDNAs, design ated muAUF1-3 and muAUF1-7, were isolated from a murine fetal cDNA lib rary, using as a probe, a fragment of the p37(AUF1) cDNA encoding RRM1 and approximately half of RRM2. The muAUF1-3 open reading frame (ORF) was very homologous to human p37(AUF1) with the greatest homology bet ween the corresponding RRMs and the C-terminal Gin-rich motif. Clone m uAUF1-7 was highly homologous to muAUF1-3, but was truncated within th e region encoding the RNP-1 box in RRM2. Clone muAUF1-3 encoded 19 ami no acids in RRM1 not encoded by either muAUF1-7 or human p37(AUF1). Su ch alterations in sequence could modify the RNA-binding properties of these proteins and have concomitant effects on ARE-directed posttransc riptional processes.