MOLECULAR COEVOLUTION OF MAMMALIAN RIBOSOMAL GENE TERMINATOR SEQUENCES AND THE TRANSCRIPTION TERMINATION FACTOR TTF-I

Both the DNA elements and the nuclear factors that direct termination of ribosomal gene transcription exhibit species-specific differences. Even between mammals-e.g., human and mouse-the termination signals are not identical and the respective transcription termination factors (T TFs) which bind to the terminator sequence are not fully interchangeab le. To elucidate the molecular basis for this species-specificity, we have cloned TTF-I from human and mouse cells and compared their struct ural and functional properties. Recombinant TTF-I exhibits species spe cific DNA binding and terminates transcription both in cell-free trans cription assays and in transfection experiments. Chimeric constructs o f mouse TTF-I and human TTF-I reveal that the major determinant for sp ecies-specific DNA binding resides within the C terminus of TTF-I. Rep lacing 31 C-terminal amino acids of mouse TTF-I with the homologous hu man sequences relaxes the DNA-binding specificity and, as a consequenc e, allows the chimeric factor to bind the human terminator sequence an d to specifically stop rDNA transcription.