Puf6 primes 60S pre-ribosome nuclear export at low temperature

Gerhardy, Stefan; Oborská-Oplová, Michaela; Gillet, Ludovic; Börner, Richard; Nues, Rob W. van; Leitner, Alexander; Michel, Erich; Petkowski, Janusz J.; Granneman, Sander; Sigel, Roland K. O.; Aebersold, Ruedi; Panse, Vikram Govind

doi:10.1038/s41467-021-24964-2

Cited by 16 publications

(21 citation statements)

References 77 publications

(127 reference statements)

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“…∆ltv 1 mutants are cold-sensitive, and the genetic interaction between LTV1 and RPS15 is also most pronounced at low temperatures. Cold-sensitive phenotypes are frequently observed upon RNA folding problems [ 54 , 55 ], hence we speculate that an altered rRNA structure occurring in the absence of Ltv1 might be the reason for the genetic interactions with Rps15.…”

Section: Discussionmentioning

confidence: 95%

The C-terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre-40S maturation

et al. 2022

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The small ribosomal subunit protein Rps15/uS19 is involved in early nucleolar ribosome biogenesis and subsequent nuclear export of pre-40S particles to the cytoplasm. In addition, the C-terminal tail of Rps15 was suggested to play a role in mature ribosomes, namely during translation elongation. Here, we show that Rps15 not only functions in nucleolar ribosome assembly but also in cytoplasmic pre-40S maturation, which is indicated by a strong genetic interaction between Rps15 and the 40S assembly factor Ltv1. Specifically, mutations either in the globular or C-terminal domain of Rps15 when combined with the non-essential ltv1 null allele are lethal or display a strong growth defect. However, not only rps15 ltv1 double mutants but also single rps15 C-terminal deletion mutants exhibit an accumulation of the 20S pre-rRNA in the cytoplasm, indicative of a cytoplasmic pre-40S maturation defect. Since in pre-40S particles, the C-terminal tail of Rps15 is positioned between assembly factors Rio2 and Tsr1, we further tested whether Tsr1 is genetically linked to Rps15, which indeed could be demonstrated. Thus, the integrity of the Rps15 C-terminal tail plays an important role during late pre-40S maturation, perhaps in a quality control step to ensure that only 40S ribosomal subunits with functional Rps15 C-terminal tail can efficiently enter translation. As mutations in the C-terminal tail of human RPS15 have been observed in connection with chronic lymphocytic leukaemia, it is possible that apart from defects in translation, an impaired late pre-40S maturation step in the cytoplasm could also be a reason for this disease.

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Section: Discussionmentioning

confidence: 95%

The C-terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre-40S maturation

et al. 2022

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“…Following synthesis of ribosomal subunit precursors in the nucleus, they need to enter the cytoplasm via the nuclear pore prior to combining with RPs to complete the maturation process. Gerhardy and his colleagues reported that the low temperature induced assembly protein, Puf6, primed 60S pre-ribosome nuclear exportation and intervened rRNA compaction, was a momentous temperature-regulated rescuing mechanism underlying countering rRNA misfolding and priming exportation competence 37 . Meanwhile, dedicated chaperones specifically mediate the transportation of RPs to ensure the successful implementation of this process.…”

Section: Ribosome Quality Control Systemmentioning

confidence: 99%

Eukaryotic ribosome quality control system: a potential therapeutic target for human diseases

Zhao¹,

Yao²,

Zhang³

et al. 2022

Int. J. Biol. Sci.

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Protein homeostasis is well accepted as the prerequisite for proper operation of various life activities. As the main apparatus of protein translation, ribosomes play an indispensable role in the maintenance of protein homeostasis. Nevertheless, upon stimulation of various internal and external factors, malfunction of ribosomes may be evident with the excessive production of aberrant proteins, accumulation of which can result in deleterious effects on cellular fate and even cell death. Ribosomopathies are characterized as a series of diseases caused by abnormalities of ribosomal compositions and functions. Correspondingly, cell evolves several ribosome quality control mechanisms in maintaining the quantity and quality of intracellular ribosomes, namely ribosome quality control system (RQCS). Of note, RQCS can tightly monitor the entire process from ribosome biogenesis to its degradation, with the capacity of coping with ribosomal dysfunction, including misassembled ribosomes and incorrectly synthesized ribosomal proteins. In the current literature review, we mainly introduce the RQCS and elaborate on the underlying pathogenesis of several ribosomopathies. With the in-depth understanding of ribosomal dysfunction and molecular basis of RQCS, therapeutic strategy by specifically targeting RQCS remains a promising option in treating patients with ribosomopathies and other ribosome-associated human diseases.

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“…[94] rbfA deletion strain exhibits cold-sensitivity and increased levels of an unprocessed precursor of 16S rRNA [94] Notably, in wild-type cells, RbfA is specifically induced at LT [95] suggesting that the 5′ helix of 16S rRNA requires its RNA chaperoning activity to correctly fold at LT. [96] A quantitative proteomic study from our laboratory revealed how the yeast ribosome assembly pathway is rewired to adapt to LT. We found that yeast cells globally induce production of r-proteins and AFs when grown at LT as compared to optimal temperatures. [97] Notably, a significant group of induced proteins were ATP-dependent RNA helicases and components associated with C/D box snoRNAs. [97] An rRNA chaperoning function for snoRNAs has been suggested, [54,98] raising the possibility of whether their induction at LT also facilitates pre-rRNA folding during ribosome assembly under challenging circumstances.…”

Section: Rna Folding At Low Temperaturementioning

confidence: 99%

“…[97] Notably, a significant group of induced proteins were ATP-dependent RNA helicases and components associated with C/D box snoRNAs. [97] An rRNA chaperoning function for snoRNAs has been suggested, [54,98] raising the possibility of whether their induction at LT also facilitates pre-rRNA folding during ribosome assembly under challenging circumstances.…”

Section: Rna Folding At Low Temperaturementioning

confidence: 99%

“…Deletion or perturbation of the RNA-binding platform of Puf6 induced a cold-sensitive growth phenotype and impaired 60S pre-ribosome nuclear export. A combination of biochemistry, cell biology and ensemble Förster resonance energy transfer (FRET) studies revealed a critical RNA chaperoning function for Puf6 at LT. [97] Puf6 contains an atypical Pumilio repeat RNA-binding domain with 11 PUM repeats, which was previously shown to bind to ssRNA and dsRNA without F I G U R E 6 Gradual rRNA compaction of the 60S pre-ribosome from the nucleolus to the cytoplasm. 60S pre-ribosome compacts in a modular fashion starting with the domain I and II intertwined with 5.8S and internal transcribed spacer 2 (ITS2; PDB ID: 6EM3).…”

Section: Rna Folding At Low Temperaturementioning

confidence: 99%

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Orchestrating ribosomal RNA folding during ribosome assembly

2022

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Construction of the eukaryotic ribosome is a complex process in which a nascent ribosomal RNA (rRNA) emerging from RNA Polymerase I hierarchically folds into a native three-dimensional structure. Modular assembly of individual RNA domains through interactions with ribosomal proteins and a myriad of assembly factors permit efficient disentanglement of the error-prone RNA folding process. Following these dynamic events, long-range tertiary interactions are orchestrated to compact rRNA. A combination of genetic, biochemical, and structural studies is now providing clues into how a nascent rRNA is transformed into a functional ribosome with high precision. With this essay, we aim to draw attention to the poorly understood process of establishing correct RNA tertiary contacts during ribosome formation. K E Y W O R D Sco-transcriptional ribosome assembly, low temperature, modular rRNA compaction, RNA folding, RNA-binding proteins THE COMPLEX VERSATILE STRUCTURE OF RNALike DNA, the RNA polymer consists of basic units called nucleotides.

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Puf6 primes 60S pre-ribosome nuclear export at low temperature

Cited by 16 publications

References 77 publications

The C-terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre-40S maturation

The C-terminal tail of ribosomal protein Rps15 is engaged in cytoplasmic pre-40S maturation

Eukaryotic ribosome quality control system: a potential therapeutic target for human diseases

Orchestrating ribosomal RNA folding during ribosome assembly

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