Regulation of ribonucleotide reductase during iron limitation

Abstract

In this issue of Molecular Cell, Sanvisens et al. (2011) report a new mechanism for regulation of yeast ribonucleotide reductase activity that occurs during iron deprivation.

Figure 1. Regulation of RNR activity during iron limitation

RNR activity in iron-replete conditions is limited by the physical separation of the two subunits of the RNR enzyme. A homodimer of Rnr1 (R1) containing the catalytic domain resides in the cytosol while the iron-containing heterodimer Rnr2-Rnr4 (R2) is tethered in the nucleus through binding to Wtm1. Upon iron limitation there is increased transcription of the mRNA binding proteins Cth1 and Cth2. These proteins bind to specific sequences in the 3’region of WTM1 mRNA, which targets that mRNA for degradation leading to decreased levels of Wtm1. The loss of Wtm1 releases R2 from the nucleus permitting it to translocate to the cytosol, bind to R1 forming an active enzyme.