TIF-IA, the factor mediating growth-dependent control of ribosomal RNA synthesis, is the mammalian homolog of yeast Rrn3p.
Cells carefully modulate the rate of rRNA transcription in order to prevent an overinvestment in ribosome synthesis under less favorable nutritional conditions. In mammals, growth-dependent regulation of RNA polymerase I (Pol I) transcription is mediated by TIF-IA, an essential initiation factor that is active in extracts from growing but not starved or cycloheximide-treated mammalian cells. Here we report the molecular cloning and functional characterization of recombinant TIF-IA, which turns out to be the mammalian homolog of the yeast factor Rrn3p. We demonstrate that TIF-IA interacts with Pol I in the absence of template DNA, augments Pol I transcription in vivo and rescues transcription in extracts from growth-arrested cells in vitro.
Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg.
J
J
Bodem
G
G
Dobreva
U
U
Hoffmann-Rohrer
S
S
Iben
H
H
Zentgraf
H
H
Delius
M
M
Vingron
I
I
Grummt
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015003:Yeasts / Q000235:genetics
D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; C101161:RRN3 protein, S cerevisiae; C428423:RRN3 protein, human; C491074:Rrn3 protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors