Oxygen and lipid homeostases require the sterol regulatory element-binding protein (Sre1) in Schizosaccharomyces pombe. Sre1 is cleaved to release the N-terminal basichelix-loop-helix (bHLH) transcription factor Sre1N when oxygen or ergosterol levels fall. Sre1N is regulated by the import adaptor Nro1 and the prolyl dihydroxylase Ofd1,together with the Ofd1 substrate, pre-ribosomal uS12/Rps23. This dissertation shows that Nro1 imports Rps23 with Ofd1. The Ofd1-Rps23-Nro1 complex is stabilized when Ofd1is unable to dihydroxylate Rps23 P62, a condition that occurs during hypoxia. As a result, Ofd1 is prevented from down-regulating Sre1N under low oxygen. In support of this model, I identified a common Ofd1 binding site in Nro1, Rps23, and Sre1N, and show that Ofd1-dependent dihydroxylation of Rps23 P62 is aberrant in the absence of Nro1. Since ribosomal protein expression and ribosome biogenesis respond to cellular growth conditions, this mechanism, in theory, allows the nutritional state to tune Sre1 signaling by controlling Ofd1 availability. Finally, my work provides a paradigm for how other ribosomal oxidases may function.
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THE REGULATION OF HYPOXIC ADAPTATION THROUGH COUPLED PROLYL DIHYDROXYLATION AND NUCLEAR IMPORT OF PRE-RIBOSOMAL uS12/RPS23 IN FISSION YEAST