TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes

Sunil Shetty1, Jon Hofstetter1, Stefania Battaglioni1

  • 1Biozentrum, University of Basel, Basel, Switzerland.

The EMBO Journal
|January 24, 2023
PubMed

Insights

Target of rapamycin complex 1 (TORC1) regulates ribosome dormancy. Stm1 protein preserves dormant ribosomes under nutrient limitation, and TORC1 directly inhibits Stm1 to resume translation, a conserved mechanism.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Target of rapamycin complex 1 (TORC1) controls ribosome biogenesis and degradation based on nutrient availability.
  • Cells maintain dormant ribosomes during nutrient scarcity, but their regulation is unclear.

Purpose of the Study:

  • To investigate the regulation of dormant ribosomes under nutrient-limited conditions.
  • To elucidate the role of the ribosome preservation factor Stm1 in TORC1-mediated ribosome regulation.

Main Methods:

  • Yeast genetics and molecular biology techniques.
  • Rapamycin treatment and nitrogen starvation to inhibit TORC1.
  • Analysis of ribosome formation, translation status, and degradation.

Main Results:

  • TORC1 inhibition induces Stm1-mediated formation of dormant 80S ribosomes.
  • Stm1 protects these dormant ribosomes from proteasomal degradation.
  • TORC1 directly phosphorylates and inhibits Stm1 upon nutrient refeeding, reactivating translation.
  • Mammalian SERBP1 acts similarly to Stm1, indicating conserved regulation.

Conclusions:

  • TORC1 directly regulates ribosomal dormancy through the ribosome preservation factor Stm1.
  • This mechanism of regulating dormant ribosomes is conserved across yeast and mammals.
  • Stm1 is a key mediator of ribosome preservation under nutrient stress.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.3K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
66
Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
75