NUFIP1 is a ribosome receptor for starvation-induced ribophagy

Wyant, Gregory A.; Abu-Remaileh, Monther; Frenkel, Evgeni M.; Laqtom, Nouf N.; Dharamdasani, Vimisha; Lewis, Caroline A.; Chan, Sze Ham; Heinze, Ivonne; Ori, Alessandro; Sabatini, David M.

doi:10.1126/science.aar2663

Cited by 271 publications

(257 citation statements)

References 53 publications

(56 reference statements)

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“…Therefore, we introduced a measure of charge conservation (see Methods) that specifically accounts for the local presence of positively charged amino acids in an alignment. Recent studies have shown enrichment of positively charged amino acids in ribosomal proteins [32]. Upon computing the charge score for our sequence alignments, we indeed found some significant correlation between the sequence conservation and charge conservation scores for bacterial proteins with Pearson's correlation r 2 = 0.70, 0.51 and 0.47 (p-values < 10 −4 ) for bacterial alignments of uL4, uL23 and uL22, respectively (see Supplementary Data).…”

Section: Conservation Of Ribosomal Protein Sequence and Positive Charsupporting

confidence: 52%

Differences in the path to exit the ribosome across the three domains of life

Duc

Batra

Bhattacharya

et al. 2018

Preprint

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Recent advances in biological imaging have led to a surge of fine-resolution structures of the ribosome from diverse organisms. Comparing these structures, especially the exit tunnel, to characterize the key similarities and differences across species is essential for various important applications, such as designing antibiotic drugs and understanding the intricate details of translation dynamics. Here, we compile and compare 20 fine-resolution cryo-EM and X-ray crystallography structures of the ribosome recently obtained from all three domains of life (bacteria, archaea and eukarya). We first show that a hierarchical clustering of tunnel shapes closely reflects the species phylogeny. Then, by analyzing the ribosomal RNAs and proteins localized near the tunnel, we explain the observed geometric variations and show direct association between the conservations of the geometry, structure, and sequence. We find that the tunnel is more conserved in its upper part, from the polypeptide transferase center to the constriction site. In the lower part, tunnels are significantly narrower in eukaryotes than in bacteria, and we provide evidence for the existence of a second constriction site in eukaryotic tunnels. We also show that ribosomal RNA and protein sequences are more likely to be conserved closer to the tunnel, as is the presence of positively charged amino acids. Overall, our comparative analysis shows how the geometric and biophysical properties of the exit tunnel play an important role in ensuring proper transit of the nascent polypeptide chain, and may explain the differences observed in several co-translational processes across species.

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Section: Conservation Of Ribosomal Protein Sequence and Positive Charsupporting

confidence: 52%

Differences in the path to exit the ribosome across the three domains of life

Duc

Batra

Bhattacharya

et al. 2018

Preprint

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“…Multimodal analysis of mitochondria from specific cell types will be important for trying to dissect mitochondrial heterogeneity in complex tissues, such as the brain and kidney. Furthermore, the ability to rapidly isolate mitochondria from specific cell-types without the need for cell sorting and long centrifugation steps can reduce the magnitude of distortion of the original mitochondrial state, as well as significantly decrease the time and effort needed to acquire the desired mitochondrial material, which can be useful for not just metabolomic but also proteomic work by better preserving the native proteomic mitochondrial profile and the interactions of proteins that peripherally associate with mitochondrial membranes (22). Of note, the design of our in vivo workflow is such that it can also be combined with other downstream studies aside from those utilized here, such as genomic and transcriptomic analyses.…”

Section: Discussionmentioning

confidence: 99%

MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo

Bayraktar

Baudrier

Özerdem

et al. 2018

Preprint

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Mitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific celltypes within mammalian tissues have been limited. To address this, we built on prior work in which we exploited a mitochondrially-localized 3XHA epitope-tag ("MITO-Tag") for the fast isolation of mitochondria from cultured cells to now generate "MITO-TagMice." Affording spatiotemporal control over MITO-Tag expression, these transgenic animals enable the rapid, cell-type-specific immunoisolation of mitochondria from tissues, which we verified using a combination of proteomic and metabolomic approaches. Using MITO-Tag Mice and targeted and untargeted metabolite profiling, we identified changes during fasted and refed conditions in a diverse array of mitochondrial metabolites in hepatocytes and found metabolites that behaved differently at the mitochondrial versus whole-tissue level. MITO-Tag Mice should have utility for studying mitochondrial physiology and our strategy should be generally applicable for studying other mammalian organelles in specific cell-types in vivo.

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“…At a more global level, our study shows how protein levels can be more or less robust against changes in the ribosomal pool, which can simultaneously affect all initiation rates in a cell. Since the level of ribosomes present in a cell fluctuates over time [29], it would be interesting to see if protein levels scale uniformly with these variations across genes, and if not, whether the differences in λ 0 can explain it.…”

Section: Discussionmentioning

confidence: 99%

The key parameters that govern translation efficiency

Erdmann-Pham

Duc

Song

2018

Preprint

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Translation of mRNA into protein is a fundamental yet complex biological process with multiple factors that can potentially affect its efficiency. In particular, different genes can have quite different initiation rates, while site-specific elongation rates can vary substantially along a given transcript. Here, we analyze a stochastic model of translation dynamics to identify the key parameters that govern the overall rate of protein synthesis and the efficiency of ribosome usage. The mathematical model we study is an interacting particle system that generalizes the Totally Asymmetric Simple Exclusion Process (TASEP), where particles correspond to ribosomes. While the TASEP and its variants have been studied for the past several decades through simulations and mean field approximations, a general analytic solution has remained challenging to obtain. By analyzing the so-called hydrodynamic limit, we here obtain exact closed-form expressions for stationary currents and particle densities that agree well with Monte Carlo simulations. In addition, we provide a complete characterization of phase transitions in the system. Surprisingly, phase boundaries depend on only four parameters: the particle size, and the first, last and minimum particle jump rates. Relating these theoretical results to translation, we formulate four design principles that detail how to tune these parameters to optimize translation efficiency in terms of protein production rate and resource usage. We then analyze ribosome profiling data of S. cerevisiae and demonstrate that its translation system is generally efficient, consistent with the design principles we found. We discuss implications of our findings on evolutionary constraints and codon usage bias.

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NUFIP1 is a ribosome receptor for starvation-induced ribophagy

Cited by 271 publications

References 53 publications

Differences in the path to exit the ribosome across the three domains of life

Differences in the path to exit the ribosome across the three domains of life

MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo

The key parameters that govern translation efficiency

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