Regulation, evolution and consequences of cotranslational protein complex assembly

Natan, Eviatar; Wells, Justin; Teichmann, Sarah A.; Marsh, Joseph A.

doi:10.1016/j.sbi.2016.11.023

Cited by 66 publications

(65 citation statements)

References 70 publications

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“…at the N- rather than C-terminus, increases the propensity for assembly to occur during, or soon after translation. Although such early assembly may be beneficial for some proteins6,23, it can also lead to misassembly due to an increase in nonspecific interactions between partially unfolded nascent chains (Figure 1). …”

Section: Resultsmentioning

confidence: 99%

“…For homomeric proteins the relationship between these parameters is only partially understood4,6,42. The stability of the monomer, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Homomers are common in all organisms, particularly prokaryotes, and are involved in all major cellular functions4,5. If a homomeric nascent chain folds during or soon after translation, it may start assembly6,7. We have coined the term translational milieu to describe the environment around a transcript that is being translated by ribosomes.…”

Section: Introductionmentioning

confidence: 99%

“…We have coined the term translational milieu to describe the environment around a transcript that is being translated by ribosomes. Assembly of a nascent chain can occur with ( i ) a neighboring nascent chain that is translated from the same mRNA, ( ii ) a proximal, mature subunit that was recently released from the same mRNA, or ( iii ) a nascent chain, or ( iv ) a mature protein that was translated by another copy of the mRNA 6 (Figure 1). In all these scenarios, misassembly might occur if assembly forces unfolded, partially folded or freshly folded parts of the polypeptide into extremely close proximity.…”

Section: Introductionmentioning

confidence: 99%

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Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Natan¹,

Endoh

Haim-Vilmovsky

et al. 2018

Nat Struct Mol Biol

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Cotranslational protein folding can facilitate rapid formation of functional structures. However, it might also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. By analyzing known protein structures, we show that homomeric protein contacts are enriched towards the C-termini of polypeptide chains across diverse proteomes. We hypothesize that this is the result of evolutionary constraints for folding to occur prior to assembly. Using high-throughput imaging of protein homomers in vivo in E. coli and engineered protein constructs with N- and C-terminal oligomerization domains, we show that, indeed, proteins with C-terminal homomeric interface residues consistently assemble more efficiently than those with N-terminal interface residues. Using in vivo, in vitro and in silico experiments, we identify features that govern successful assembly of homomers, which have implications for protein design and expression optimization.

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Section: Resultsmentioning

confidence: 99%

“…For homomeric proteins the relationship between these parameters is only partially understood4,6,42. The stability of the monomer, i.e.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Natan¹,

Endoh

Haim-Vilmovsky

et al. 2018

Nat Struct Mol Biol

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“…Similarly, targeting myelin basic protein mRNA to the distal ends of oligodendrocytes is important to prevent unwanted membrane fusion events . The localized translation of mRNAs encoding functionally‐associated proteins may also yield more efficient protein complex assembly . One of the earliest examples of this occurrence was depicted in the amoeba, where it was found that the mRNAs of the components that make up the basal body and flagella were co‐localized to the cell periphery .…”

Section: Biological Functions and Prevalence Of Rna Localizationmentioning

confidence: 99%

Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways

et al. 2018

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The asymmetric subcellular distribution of RNA molecules from their sites of transcription to specific compartments of the cell is an important aspect of post-transcriptional gene regulation. This involves the interplay of intrinsic cis-regulatory elements within the RNA molecules with trans-acting RNAbinding proteins and associated factors. Together, these interactions dictate the intracellular localization route of RNAs, whose downstream impacts have wide-ranging implications in cellular physiology. In this review, we examine the mechanisms underlying RNA localization and discuss their biological significance. We also review the growing body of evidence pointing to aberrant RNA localization pathways in the development and progression of diseases.Keywords: Cis-regulatory elements; RNA disease; RNA localization; RNA-binding proteinsThe asymmetric organization of cells is a pervasive feature that ensures the homeostasis of prokaryotic and eukaryotic organisms. This relies on the capacity of cells to organize their contents, including lipids, nucleic acids, and proteins, into specific subcellular structures and organelles. While much of this organization has been attributed to subcellular protein transport [1], a growing body of work indicates that the regulated localization of RNA molecules is also a key process observed across evolutionary timescales [2][3][4][5][6]. This form of post-transcriptional regulation where coding and noncoding RNA molecules actively associate with trans-acting partners, such as RNA-binding proteins (RBPs), serves to dictate both the function and intra-or extracellular destiny of the RNA. During RNA localization, cis-regulatory elements found within the RNA molecule, whether coding or noncoding, act as recognition sites for the recruitment of trans-acting RBPs, which dictate the intra-/extra-cellular fate of the RNA and, ultimately, its functional state. Over the years, the wide-ranging implications of RNA localization on cellular physiology have become apparent, affecting many aspects of cell organization and function. Indeed, RNA localization pathways have been linked to numerous important processes, including developmental patterning, cell polarity, spindle assembly, formation of nonmembranous compartments, localized translation, and cell motility [2][3][4][5][6].

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Biogenic Imaging Contrast Agents

et al. 2023

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Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly important role in biomedical research ranging from subcellular level to individual level. The unique properties of BICAs, including expression by cells as reporters and specific genetic modification, facilitate various in vitro and in vivo studies, such as quantification of gene expression, observation of protein interactions, visualization of cellular proliferation, monitoring of metabolism, and detection of dysfunctions. Furthermore, in human body, BICAs are remarkably helpful for disease diagnosis when the dysregulation of these agents occurs and can be detected through imaging techniques. There are various BICAs matched with a set of imaging techniques, including fluorescent proteins for fluorescence imaging, gas vesicles for ultrasound imaging, and ferritin for magnetic resonance imaging. In addition, bimodal and multimodal imaging can be realized through combining the functions of different BICAs, which helps overcome the limitations of monomodal imaging. In this review, the focus is on the properties, mechanisms, applications, and future directions of BICAs.

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Regulation, evolution and consequences of cotranslational protein complex assembly

Cited by 66 publications

References 70 publications

Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Biological functions, regulatory mechanisms, and disease relevance of RNA localization pathways

Biogenic Imaging Contrast Agents

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