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The Codependent Expression of the Essential Mammalian RNA Polymerase I PAF49/PAF53 Heterodimer

Ribosome biogenesis (RB) is a complex process that plays a central role in maintaining cellular homeostasis and supporting cell growth. Therefore, dysregulation of RB contributes to pathologies such as cancer, ribosomopathies, neurodegenerative diseases, and aging. Our lab studies transcription of ribosomal RNA by RNA polymerase I (Pol I), the rate‐limiting step in ribosome biogenesis. Many studies have demonstrated that inhibiting Pol I transcription in cancer cells causes cell death while untransformed cells arrest, thereby making the Pol I apparatus a target for chemotherapeutic agents. This study focuses on two mammalian polymerase associated factors of the Pol I transcription apparatus, PAF49 and PAF53. The PAFs form a heterodimeric complex and are required for rDNA transcription and cell proliferation. The goal of this study is to determine the role(s) of PAF49 and PAF53 in rDNA transcription and understand how these two proteins are regulated.