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

Abstract

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.