STRUCTURE, TISSUE DISTRIBUTION AND GENOMIC ORGANIZATION OF THE MURINERRM-TYPE RNA-BINDING PROTEINS TIA-1 AND TIAR

TIA-1 and TIAR are RNA binding proteins of the RNA recognition motif ( RRM)/ribonucleoprotein (RNP) family that have been implicated as effec ters of apoptotic cell death, We report the structures of murine TIA-1 and TIAR (mTIA-1 and mTIAR) deduced from cDNA cloning, the mRNA and p rotein tissue distribution of mTIA-1 and mTIAR, and the exon-intron st ructures of the mTIA-1 and mTIAR genes. Both mTIA-1 and mTIAR are comp rised of three similar to 100 amino acid N-terminal RRM domains and a similar to 90 amino acid C-terminal auxiliary domain, This subfamily o f RRM proteins is evolutionarily well conserved; mTIA-1 and mTIAR are 80% similar to each other, and 96 and 99% similar to hTIA-1 and hTIAR, respectively, The overall exon-intron structures of the mTIA-1 and mT IAR genes are also similar to each other, as well as to the human TIA- 1 gene structure, While Northern blot analysis reveals that mTIA-1 and mTIAR mRNAs have a broad tissue distribution, mTIA-1 and mTIAR protei ns are predominantly expressed in brain, testis and spleen, At least t wo isoforms of both mTIA-1 and mTIAR are generated by alternative spli cing, Murine TIA-1 isoforms including or lacking the exon 5 encoded se quences are expressed at a ratio of similar to 1:1, whereas mTIAR isof orms including or lacking the 5'-end of exon 3 sequences are expressed in a similar to 1:6 ratio, Molecular characterization of murine TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analys is of the functional roles of these proteins during mammalian developm ent.