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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
Tor1 and CK2 kinases control a switch between alternative ribosome biogenesis pathways in a growth-dependent manner
Isabelle C Kos-Braun1, Ilona Jung1, Martin Koš1
1Biochemistry Center, University of Heidelberg, Heidelberg, Germany.
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.
Insights
The Target of rapamycin 1 (Tor1) pathway controls ribosome production during stress. This study reveals Tor1 and casein kinase 2 (CK2) regulate pre-ribosomal RNA processing post-transcriptionally, halting new ribosome synthesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Ribosome biogenesis is a critical, energy-intensive cellular process.
- The Target of rapamycin 1 (Tor1) pathway is known to regulate ribosomal RNA (rRNA) synthesis transcriptionally.
- The posttranscriptional regulation of ribosome biogenesis remains largely uncharacterized.
Purpose of the Study:
- To investigate the posttranscriptional control mechanisms of ribosome biogenesis.
- To determine the role of Tor1 and casein kinase 2 (CK2) in regulating pre-ribosomal RNA (pre-rRNA) processing.
- To identify novel signaling pathways involved in ribosome biogenesis regulation under stress conditions.
Main Methods:
- Utilized yeast as a model organism.
- Investigated the effects of Tor1 and CK2 kinases on pre-rRNA processing pathways.
- Analyzed the role of Sch9 kinase in the stress-induced regulation of ribosome biogenesis.
Main Results:
- Demonstrated that Tor1 and CK2 kinases control a rapid switch in pre-rRNA processing pathways in yeast.
- Showed that under stress, pre-rRNA synthesis continues but is processed into non-productive forms, halting ribosome production.
- Found that this regulatory switch is independent of Sch9 kinase activity.
Conclusions:
- Identified a novel TOR Complex 1 (TORC1) signaling pathway involving CK2 that directly regulates ribosome biogenesis at the posttranscriptional level.
- Established that Tor1 and CK2 kinases mediate a rapid response to cellular stress by altering pre-rRNA processing.
- Highlighted a previously unrecognized mechanism for controlling ribosome production independent of transcriptional regulation and Sch9 kinase.
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