Oligomerization of the transcription termination factor TTF-I: implications for the structural organization of ribosomal transcription units.

Mammalian ribosomal genes are flanked at their 5'and 3'ends by terminator sequences which are recognized by the transcription termination factor TTF-I. The occurrence of the same binding site upstream and downstream of the gene raises the possibility that TTF-I can interact with both sequences simultaneously and thus brings the terminator in the vicinity of the gene promoter by looping out the pre-rRNA coding sequence. To test this model, we have examined the ability of TTF-I to oligomerize and found that both full-length and N-terminally truncated versions of TTF-I form stable oligomeric structures. At least two domains of TTF-I located within the 184 N-terminal and 445 C-terminal amino acids, respectively, mediate the self-association of several TTF-I molecules. In support of the looping model, TTF-I is capable of linking two separate DNA fragments via binding to the target sites. This result indicates that in addition to its function in transcription termination, TTF-I may serve a role in the structural organization of the ribosomal genes which may be important for maintaining the high loading density of RNA polymerase I on active rRNA genes.