Identification of novel genes encoding transcription elongation factor TFIIS (TCEA) in vertebrates: conservation of three distinct TFIIS isoforms in frog, mouse, and human.

We report the characterization of cDNA clones that define a new, third isoform of the transcription elongation factor TFIIS in Xenopus, mouse, and human. In Xenopus the mRNA of this isoform, termed TFIIS.h, shows tissue-restricted expression, frequently contains unspliced introns, and is characterized by three near-perfect 150-bp repeats at the 5'-terminus. Although we were unable to isolate full-length cDNAs, it is clear that these repeats contain an open reading frame encoding a region of TFIIS.h that is much more complex than in other isoforms. Identification of ESTs encoding TFIIS.h in mouse and human followed by the sequencing of cognate cDNA clones enabled the complete TFIIS.h coding region to be predicted. The conserved N- and C-terminal domains of mammalian TFIIS.h (TCEA3) are separated by a linker region that is more variable in sequence and that is also 50 amino acids longer than in other isoforms. The repetitive region of Xenopus TFIIS.h apparently corresponds to an even more extended linker. Phylogenetic analysis of TFIIS sequences demonstrates the ancient origins of the three vertebrate isoforms, although they appeared functionally equivalent in in vitro RNA cleavage assays.