Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint

Abstract

In the yeast Saccharomyces cerevisiae it has long been thought that cells must reach a critical cell size, called the “setpoint,” in order to allow the Start cell cycle transition. Recent evidence suggests that this setpoint is lowered when ribosome biogenesis is slowed. Here we present evidence that yeast can sense ribosome biogenesis independently of mature ribosome levels and protein synthetic capacity. Our results suggest that ribosome biogenesis directly promotes passage through Start through Whi5, the yeast functional equivalent to the human tumor suppressor Rb. When ribosome biogenesis is inhibited, a Whi5-dependent mechanism inhibits passage through Start before significant decreases in both the number of ribosomes and in overall translation capacity of the cell become evident. This delay at Start in response to decreases in ribosome biogenesis occurs independently of Cln3, the major known Whi5 antagonist. Thus ribosome biogenesis may be sensed at multiple steps in Start regulation. Ribosome biogenesis may thus both delay Start by increasing the cell size setpoint and independently may promote Start by inactivating Whi5.

Powering through ribosome assembly

“…Examples of cross talk between ribosome assembly and other cellular processes mediated through shared components include replication, rRNA transcription, tRNA export, cell cycle control, and stress response (e.g., Angermayr and Bandlow 2002;Du and Stillman 2002;Steiner-Mosonyi et al 2003;Killian et al 2004;Bernstein et al 2007;Rudra et al 2007;Strub et al 2007;Jwa et al 2008), and this cross talk is more evolved in higher organisms. Because the connection to the cell cycle has been recently and expertly reviewed (Dez and Tollervey 2004;, it will not be covered here.…”

Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36

“…8). Several studies in yeast and human cells have suggested a checkpoint control system that senses the cellular activity to newly synthesize ribosomes, independently of the level of pre-existing ribosomes (Oeffinger and Tollervey, 2003;Zhang et al, 2003;Bernstein et al, 2007). Another even more likely possibility, therefore, is that cells stalled in cell division when they were deficient in ribosome biogenesis in the absence of USP36.…”

Role of GTPases in ribosome assembly

“…[64][65][66] Conversely, because protein synthesis and growth is only desirable under favorable cellular conditions, ribosome synthesis is highly responsive to growth conditions, including nutrient availability, heat and cold shock, as well as oxidative stress. [67][68][69][70][71] The mechanisms underlying these regulatory steps are poorly understood.…”