Tor1 and CK2 kinases control a switch between alternative ribosome biogenesis pathways in a growth-dependent manner.

Isabelle C Kos-Braun,Ilona Jung,Martin Koš,Tom Misteli

doi:10.1371/journal.pbio.2000245

Abstract

Ribosome biogenesis is a major energy-consuming process in the cell that has to be rapidly down-regulated in response to stress or nutrient depletion. The target of rapamycin 1 (Tor1) pathway regulates synthesis of ribosomal RNA (rRNA) at the level of transcription initiation. It remains unclear whether ribosome biogenesis is also controlled directly at the posttranscriptional level. We show that Tor1 and casein kinase 2 (CK2) kinases regulate a rapid switch between a productive and a non-productive pre-rRNA processing pathways in yeast. Under stress, the pre-rRNA continues to be synthesized; however, it is processed differently, and no new ribosomes are produced. Strikingly, the control of the switch does not require the Sch9 kinase, indicating that an unrecognized Tor Complex 1 (TORC1) signaling branch involving CK2 kinase directly regulates ribosome biogenesis at the posttranscriptional level.

Highlights

All cells must adapt to a constantly changing environment in order to maintain their intracellular equilibrium and to balance growth with survival
Ribosome biogenesis is highly dynamic and complex and requires the coordinated action of myriads of factors and RNAs. It begins with the synthesis of the precursor ribosomal RNA, which is concurrently cleaved, modified, folded, and assembled together with ribosomal proteins into mature ribosomal subunits
We reveal that yeast rapidly switches to an alternative ribosomal RNA (rRNA) processing pathway, in which the precursor rRNA is cleaved differently and the ribosome biogenesis is arrested at a distinct stage

Summary

Introduction

All cells must adapt to a constantly changing environment in order to maintain their intracellular equilibrium and to balance growth with survival. When essential nutrients become unavailable, cell division is arrested at the G1 phase of the cell cycle, cells change metabolism, and prepare for entry into the reversible quiescent/G0 state, in which they can survive for decades (reviewed in [1]). The diauxic shift occurs when glucose becomes depleted from the media and yeast switches to respiratory metabolism concomitantly with a sharp decrease in growth rate. In the subsequent postdiauxic phase, yeast grows at a much slower rate, using respiration to provide energy, and starts to acquire characteristic features of stationary cells until the growth ceases completely and cells become quiescent [2]. An interconnected signaling network of key kinases, the target of rapamycin complex 1 (TORC1), protein kinase A (PKA), sucrose non-fermenting 1 (Snf1p), and phosphate metabolism 85 (Pho85p), monitors the nutrient availability in yeast. While the initial transcriptional response to limitation of individual nutrients differs [4,5], there is a common core program for preparation of entry into quiescence, regardless of the limiting nutrient [1]

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Discussion

Conclusion