The Tgif2 gene contains a retained intron within the coding sequence

By PCR from mouse cDNA, we identified two alternate splice forms of the Tgif2 gene. One splice variant encodes the full length 237 amino acid Tgif2, whereas the shorter form results in the removal of 39 codons from the centre of the coding region. The generation of this alternate splice form occurs with the mouse RNA, but not the human, and both splice forms are present in all mouse tissues analyzed. Human and mouse Tgif2 coding sequences contain a retained intron, which in mouse Tgif2 is removed by splicing from around 25–50% of RNAs, as assessed by RT-PCR. This splicing event is dependent on sequences within the mouse Tgif2 coding sequence. Both splice forms of mouse Tgif2 encode proteins which are active transcriptional repressors, and can repress both TGFβ dependent and independent transcription. In addition, we show that human and mouse Tgif2 interact with the transcriptional corepressor mSin3.These data demonstrate that the Tgif2 gene contains a retained intron, within the second coding exon. This retained intron is not removed from the human mRNA at a detectable level, but is spliced out in a significant proportion of mouse RNAs. This alternate splicing is dependent entirely on sequences within the mouse Tgif2 coding sequence, suggesting the presence of an exonic splicing enhancer. Both splice forms of mouse Tgif2 produce proteins which are functional transcriptional repressors.TGIF (thymine guanine interacting factor) is a homeodomain containing protein which was first identified by its ability to bind adjacent to a specific retinoic acid response element [1]. TGIF is a transcriptional repressor, which interacts with general corepressors, including CtBP and the mSin3A/histone deacetylase (HDAC) complex [2-5]. Loss of function mutations in human TGIF are associated with holoprosencephaly (HPE), a severe genetic disease affecting craniofacial development [6-8]. A human TGIF related protein (TGIF2) has been identified, which shares at least some functions with