Two forms of the large tumor suppressor gene (Lats1) protein expressed in the vertebrate retina.

The large tumor suppressor gene (Lats1) encodes a protein kinase that is highly conserved from fly to human, and plays a crucial role in the prevention of tumor formation by controlling mitosis progression. We have found that in addition to the previously isolated 7.5 kb long form of Lats1 (Lats1L) mRNA, a less abundant, shorter, 3.4 kb primary transcript (Lats1S) also is expressed in the vertebrate retina. Compared to Lats1L, the sequence of Lats1S mRNA has a deletion of exons 6, 7, and 8 that corresponds to 792 bp of the open reading frame. Thus, 264 aa of the C-terminal region of the long transcript are missing in the Lats1S protein. The encoded truncated protein lacks four of eleven conserved kinase domains and the C-terminus. Our results suggest that the 3.4 kb transcript is a splice variant of the 7.5 kb transcript. We have found direct evidence that both the retinal 7.5 and 3.4 kb mRNAs are translated into 170 kDa and 120 kDa proteins, respectively. The expression of both isoforms in vertebrate cells raises the possibility that these Lats1 proteins may act as negative key regulators of the cell cycle, each of them performing a unique role.