Redefining the Translational Status of 80S Monosomes

Heyer, Erin E.; Moore, Melissa J.

doi:10.1016/j.cell.2016.01.003

Cited by 194 publications

(209 citation statements)

References 54 publications

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“…1C). A recent study by Heyer and Moore has shown that a certain subset of mRNAs in Saccharomyces cerevisiae can be translated by monosomes (Heyer and Moore 2016). However, the study did not show that UPP genes are translated by monosomes.…”

Section: Differential Mrna Translation During Amino Acid Starvationcontrasting

confidence: 50%

Codon optimality controls differential mRNA translation during amino acid starvation

Saikia

Wang

Mao

et al. 2016

RNA

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It is common wisdom that codon usage bias has evolved in the selection for efficient translation, in which highly expressed genes are encoded predominantly by optimal codons. However, a growing body of evidence suggests regulatory roles for non-optimal codons in translation dynamics. Here we report that in mammalian cells, non-optimal codons play a critical role in promoting selective mRNA translation during amino acid starvation. During starvation, in contrast to genes encoding ribosomal proteins whose translation is highly sensitive to amino acid deprivation, translation of genes involved in the cellular protein degradation pathways remains unaffected. We found that these two gene groups bear different codon composition, with non-optimal codons being highly enriched in genes encoding the ubiquitin-proteasome system. Supporting the selective tRNA charging model originally proposed in Escherichia coli, we demonstrated that tRNA isoacceptors decoding rare codons are maintained in translating ribosomes under amino acid starvation. Finally, using luciferase reporters fused with endogenous gene-derived sequences, we show that codon optimality contributes to differential mRNA translation in response to amino acid starvation. These results highlight the physiological significance of codon usage bias in cellular adaptation to stress.

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Section: Differential Mrna Translation During Amino Acid Starvationcontrasting

confidence: 50%

Codon optimality controls differential mRNA translation during amino acid starvation

Saikia

Wang

Mao

et al. 2016

RNA

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“…Translation or ribosome binding of lncRNAs, which contain small ORFs (sORFs) and thus possibly produce micropeptides (Slavoff et al 2013;Ruiz-Orera et al 2014;Raj et al 2016) has been reported in multiple species, including yeast (Ingolia et al 2014;Smith et al 2014), fruit flies (Dunn et al 2013;Aspden et al 2014), zebrafish (Chew et al 2013;Bazzini et al 2014), and mammals (Chew et al 2013;Zhou et al 2013;Ingolia et al 2014;van Heesch et al 2014;Fields et al 2015;Ji et al 2015;Calviello et al 2016; for review, see Ingolia 2016). Moreover, a recent study provided evidence that a vast majority of monosomes is actively elongating and translating sORFs (Heyer and Moore 2016). Thus, ribosome binding/translation of some lncRNAs occurs and appears compatible with efficient cellular protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression

et al. 2017

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Many long noncoding RNAs (lncRNAs) are unstable and rapidly degraded in the nucleus by the nuclear exosome. An exosome adaptor complex called NEXT (nuclear exosome targeting) functions to facilitate turnover of some of these lncRNAs. Here we show that knockdown of one NEXT subunit, Mtr4, but neither of the other two subunits, resulted in accumulation of two types of lncRNAs: prematurely terminated RNAs (ptRNAs) and upstream antisense RNAs (uaRNAs). This suggested a NEXT-independent Mtr4 function, and, consistent with this, we isolated a distinct complex containing Mtr4 and the zinc finger protein ZFC3H1. Strikingly, knockdown of either protein not only increased pt/uaRNA levels but also led to their accumulation in the cytoplasm. Furthermore, all pt/uaRNAs examined associated with active ribosomes, but, paradoxically, this correlated with a global reduction in heavy polysomes and overall repression of translation. Our findings highlight a critical role for Mtr4/ZFC3H1 in nuclear surveillance of naturally unstable lncRNAs to prevent their accumulation, transport to the cytoplasm, and resultant disruption of protein synthesis.

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“…(4) Discard the supernatant and re-suspend the pellets in 10 ml ice-cold polysome profile buffer (PPB) (10 mM Tris-HCl pH 7.5, 50 mM NH 4 Cl, 10 mM MgCl 2 , 1 mM DTT, 100 µg/ml chloramphenicol) [11].…”

Section: S Aureus Cell Extract Preparationmentioning

confidence: 99%

“…Due to its aggressiveness and to the existence and proliferation of many multidrug-resistant strains, S. aureus is a major public health concern [13]. To our knowledge, only S. aureus ribosomes and not the polysomes have been studied [4,[14][15][16][17][18].…”

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confidence: 99%

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Purification, identification, and functional analysis of polysomes from the human pathogen Staphylococcus aureus

Brielle

Pinel-Marie

Chat

et al. 2017

Methods

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To cite this version:Régine Brielle, Marie-Laure Pinel-Marie, Sophie Chat, Reynald Gillet, Brice Felden. Purification, identification, and functional analysis of polysomes from the human pathogen Staphylococcus aureus. Methods, Elsevier, 2017, 117, pp.59-66. 10.1016/j.ymeth.2016 Keywords:Polysome, ribosome, translation, Staphylococcus aureus, sucrose gradient purification, translatome. AbstractPolysomes are macromolecular complexes made up of multiple ribosomes simultaneously translating a single mRNA into polypeptide chains. Together, the cellular mRNAs translated in this way are referred to 'translatome.' Translation determines a cell's overall gene expression profile. Studying translatome leads to a better understanding of the translational machinery and of its complex regulatory pathways. Given its fundamental role in cell homeostasis and division, bacterial translation is an important target for antibiotics. However, there are no detailed protocols for polysome purification from Staphylococcus aureus, the human pathogen responsible for the majority of multi-drug resistance issues. We therefore developed methods for the isolation of active polysomes, ribosomes, and ribosomal subunits, examining the purity and quality of each fraction and monitoring polysomal activity during protein synthesis. These steps are mandatory for the use of purified S. aureus polysomes and ribosomes for structural studies or for genome-scale analysis of most translated mRNAs.

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Redefining the Translational Status of 80S Monosomes

Cited by 194 publications

References 54 publications

Codon optimality controls differential mRNA translation during amino acid starvation

Codon optimality controls differential mRNA translation during amino acid starvation

An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression

Purification, identification, and functional analysis of polysomes from the human pathogen Staphylococcus aureus

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