Structure, tissue distribution and genomic organization of the murine RRM-type RNA binding proteins TIA-1 and TIAR

Abstract

TIA-1 and TIAR are RNA binding proteins of the RNA recognition motif (RRM)/ribonucleoprotein (RNP) family that have been implicated as effecters 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 protein tissue distribution of mTIA-1 and mTIAR, and the exon-intron structures of the mTIA-1 and mTIAR genes. Both mTIA-1 and mTIAR are comprised of three ~100 amino acid N-terminal RRM domains and a ~90 amino acid C-terminal auxiliary domain. This subfamily of 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 mTIAR 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 proteins are predominantly expressed in brain, testis and spleen. At least two isoforms of both mTIA-1 and mTIAR are generated by alternative splicing. Murine TIA-1 isoforms including or lacking the exon 5 encoded sequences are expressed at a ratio of ~1:1, whereas mTIAR isoforms including or lacking the 5'-end of exon 3 sequences are expressed in a ~1:6 ratio. Molecular characterization of murine TIA-1 and TIAR RNA binding proteins provides the basis for a genetic analysis of the functional roles of these proteins during mammalian development.