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RNA polymerase I transcription factor RRN3 is a conserved transcription factor essential for the initiation of ribosomal RNA (rRNA) gene transcription by RNA polymerase I. RRN3 forms a transient complex with RNA polymerase I, enabling it to recognize and bind to the rDNA promoter during transcription initiation. Structurally, RRN3 contains HEAT repeats, mediates protein–protein interactions, and its function is regulated by phosphorylation, particularly at a conserved serine-rich surface patch. This phosphorylation prevents RRN3 from interacting with RNA polymerase I, thereby repressing rRNA synthesis and cell growth. RRN3 is conserved from yeast through mammals and is known as TIF-IA in humans. It does not bind DNA in a sequence-specific manner but instead facilitates assembly of the pre-initiation complex at rDNA promoters. Due to its pivotal role in ribosome production and cell proliferation, RRN3 is regarded as a potential therapeutic target, especially in hyperproliferative diseases like cancer[1][2][3][4].
Inhibition of RRN3 function would be expected to impair Pol I-mediated rRNA synthesis, suppressing ribosome production and cell proliferation[1][2][4]
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