Exchange and stability of HeLa ribosomal proteins in vivo.

Lastick, Stanley M.; McConkey, Edwin H.

doi:10.1016/s0021-9258(17)33471-3

Cited by 160 publications

(21 citation statements)

References 25 publications

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“…These differences matched known observations and roles of ribosome subunits (Mathis et al, 2017). For example, the short half-life of RPL10 had first been reported in the 1970s, is conserved in mammals (Lastick and McConkey, 1976, and might be regulated by extensive ubiquitination {Bengsch, 2015 #8275; Mathis et al, 2017)(Figure 5). Ubiquitination was also observed for the short-lived RPS7 in Figure 5 (Bengsch et al, 2015).…”

Section: Discussionsupporting

confidence: 80%

Integrative Meta-Analysis Reveals That Most Yeast Proteins Are Very Stable

et al. 2018

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Measurements for protein half-lives in yeast Saccharomyces cerevisiae reported large discrepancies, with median values between minutes to several hours. We present a unifying analysis that provides a consistent half-life estimate, based on our re-analysis of three published and one new dataset of cells grown under similar conditions. We found that degradation of many proteins can be approximated by exponential decay. Protein disappearance was primarily driven by dilution due to cell division, with cell doubling times ranging from ~2 to 3.5 hours across the four experiments. After adjusting for doubling time, protein half-lives increased to median values between ~7.5 to ~40 hours. Half-lives correlated with cell doubling time even after adjustment, implying that slow growth also slows protein degradation. All estimates were validated by multiple means and were robust to different analysis methods. Overall, protein stability correlated with abundance and showed weak enrichment for degradation signals such as degrons and disordered regions. Long-lived proteins often functioned in oxidation-reduction and amino acid synthesis. Short-lived proteins often functioned in ribosome biogenesis. Despite some overall differences in behavior, all methods were able to resolve subtle difference in half-lives of ribosomal proteins, e.g. the short lifespan of RPL10. Finally, our results help the design of future experiments: time series measurements need to cover at least two to three cell doubling times for accurate estimates, exponential decay provides a reasonable proxy for protein stability, and it can be sufficiently estimated with four measurement points.

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Section: Discussionsupporting

confidence: 80%

Integrative Meta-Analysis Reveals That Most Yeast Proteins Are Very Stable

et al. 2018

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“…We found that free extra-ribosomal RPs are enriched in axons compared to the whole cell (Figure S3). This may partly explain the much higher frequencies of the ribosomal incorporation of newly synthesized RPs in Netrin-1-stimulated axons (Figure S5B) than those predicted from previous turnover studies performed on whole cells (Dice and Schimke, 1972;Lastick and McConkey, 1976). As Netrin-1-induced axonal RP synthesis may significantly increase the concentration of free RPs in axons, it may also elicit a transient increase in ribosome incorporation of newly synthesized RPs in axons (Figure 5).…”

Section: Discussionmentioning

confidence: 56%

“…Axons are long neuronal processes that carry out many vital specific cellular functions far from their cell bodies, including translation, and must therefore maintain their protein synthetic machinery in good order. However, because eukaryotic ribosome assembly is known to occur mainly in the nucleolus (Fromont-Racine et al, 2003;Lastick and McConkey, 1976;Peñ a et al, 2017), the physiological function of axonally synthesized RPs in a neuronal subcellular compartment far distant from the nucleus is enigmatic. Recent studies on spinal muscular atrophy (SMA) implicated a potential role for free RPs in the maintenance of ribosomes in axons (Bernabò et al, 2017;Rage et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…A number of previous studies called into question the widely held view of the ribosome as a stable molecular machine whose components remain unchangeable during its lifetime. For example, several RPs in the ribosome have higher turnover rates than other RP components, suggesting the possibility that individual RPs in the ribosome can be replaced by free cytoplasmic RPs (Lastick and McConkey, 1976;Mathis et al, 2017;Samir et al, 2018). These studies, together with the robust axonal translation of RPs, prompted us to ask whether axonal ribosomes incorporate locally synthesized RPs to maintain ribosome function far from the cell body.…”

Section: Introductionmentioning

confidence: 99%

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On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons

et al. 2019

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SummaryRibosome assembly occurs mainly in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) in axons, far away from neuronal cell bodies. Here, we report a physical and functional interaction between locally synthesized RPs and ribosomes in the axon. We show that axonal RP translation is regulated through a sequence motif, CUIC, that forms an RNA-loop structure in the region immediately upstream of the initiation codon. Using imaging and subcellular proteomics techniques, we show that RPs synthesized in axons join axonal ribosomes in a nucleolus-independent fashion. Inhibition of axonal CUIC-regulated RP translation decreases local translation activity and reduces axon branching in the developing brain, revealing the physiological relevance of axonal RP synthesis in vivo. These results suggest that axonal translation supplies cytoplasmic RPs to maintain/modify local ribosomal function far from the nucleolus in neurons.

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“…The age‐associated increases in ribosomal proteins (RP) could also have downstream effects on ribosome complex composition, as there is a rapid turnover of some RPs compared to other core components (Lastick & McConkey, 1976; Samir et al, 2018). A possible function for the presence of RPs in dendritic and axonal fractions could be to outfit the ribosome for immediate activity‐mediated alterations in translation rate (Holt & Schuman, 2013; A. S. Lee, Burdeinick‐Kerr, & Whelan, 2013).…”

Section: Protein Synthesis In the Aging Brainmentioning

confidence: 99%

Translational control in aging and neurodegeneration

Skariah

Todd

2020

WIREs RNA

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Protein metabolism plays central roles in age‐related decline and neurodegeneration. While a large body of research has explored age‐related changes in protein degradation, alterations in the efficiency and fidelity of protein synthesis with aging are less well understood. Age‐associated changes occur in both the protein synthetic machinery (ribosomal proteins and rRNA) and within regulatory factors controlling translation. At the same time, many of the interventions that prolong lifespan do so in part by pre‐emptively decreasing protein synthesis rates to allow better harmonization to age‐related declines in protein catabolism. Here we review the roles of translation regulation in aging, with a specific focus on factors implicated in age‐related neurodegeneration. We discuss how emerging technologies such as ribosome profiling and superior mass spectrometric approaches are illuminating age‐dependent mRNA‐specific changes in translation rates across tissues to reveal a critical interplay between catabolic and anabolic pathways that likely contribute to functional decline. These new findings point to nodes in posttranscriptional gene regulation that both contribute to aging and offer targets for therapy. This article is categorized under: Translation > Translation Regulation Translation > Ribosome Biogenesis Translation > Translation Mechanisms

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Exchange and stability of HeLa ribosomal proteins in vivo.

Cited by 160 publications

References 25 publications

Integrative Meta-Analysis Reveals That Most Yeast Proteins Are Very Stable

Integrative Meta-Analysis Reveals That Most Yeast Proteins Are Very Stable

On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons

Translational control in aging and neurodegeneration

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