5′-Heterogeneity of mouse Dda3 transcripts is attributed to differential initiation of transcription and alternative splicing

We have previously shown that mouse Dda3 gene is a p53 and p73 transcriptional target whose expression suppresses tumor cell growth. Here, we report the identification of multiple variants of Dda3 transcripts with diverse 5′ sequences through 5′ rapid amplification of cDNA ends (5′-RACE) and RT-PCR. Analysis by primer extension and RNase protection revealed that the 5′-heterogeneity was generated by transcription initiation at multiple sites in exon 1 and intron 1 and by alternative splicing. These transcripts, both coding and non-coding, exhibited distinct expression patterns in various adult tissues and were developmentally regulated. Furthermore, they were induced in a p53-dependent manner by various stress signals. These data demonstrated that differential initiation of transcription and alternative splicing both participate in the regulation of Dda3 gene expression.