RNA assemblages orchestrate complex cellular processes

Nielsen, Finn Cilius; Hansen, Henrik; Christiansen, Jan

doi:10.1002/bies.201500175

Cited by 21 publications

(21 citation statements)

References 85 publications

(102 reference statements)

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“…Recent studies have highlighted the role of intrinsically disordered regions (IDR) of proteins in driving formation of non-membrane bound, cellular compartments (Elbaum-Garfinkle et al, 2015, Kato et al, 2012, Feric et al, 2016, Murakami et al, 2015, Nielsen et al, 2016). Thus, we examined the sequences of coalescing glycolytic enzymes using IUPred, an algorithm used to predict intrinsically unstructured regions of proteins (Dosztanyi et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

et al. 2017

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SUMMARY Glycolysis is upregulated under conditions such as hypoxia and high energy demand to promote cell proliferation, although the mechanism remains poorly understood. We find that hypoxia in Saccharomyces cerevisiae induces concentration of glycolytic enzymes, including the Pfk2p subunit of the rate-limiting phosphofructokinase, into a single, non-membrane-bound granule termed the “glycolytic body” or “G body”. A yeast kinome screen identifies the yeast ortholog of AMP-activated protein kinase, Snf1p, as necessary for G body formation. Many G body components identified by proteomics are required for G body integrity. Cells incapable of forming G bodies in hypoxia display abnormal cell division and produce inviable daughter cells. Conversely, cells with G bodies show increased glucose consumption and decreased levels of glycolytic intermediates. Importantly, G bodies form in human hepatocarcinoma cells in hypoxia. Together, our results suggest that G body formation is a conserved, adaptive response to increase glycolytic output during hypoxia or tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

et al. 2017

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“…The principal structural and functional unit of this process is the numerous RNA-binding proteins (RBPs) that bind to RNA motifs to form ribonucleoprotein (RNP) complexes [26]. RNP complexes structurally represent the RNA operon, which allows functionally related proteins arising from different mRNAs to be jointly translated at a single cytoplasmic location [27]. The potential of RNP complexes to act dynamically and independently of the cellular environment is attributed to the mechanism called liquid demixing [28-37] that is triggered by intrinsically disordered RNA-binding proteins.…”

Section: Eukaryotic "Rna Operons"mentioning

confidence: 99%

“…The formation of RNP complexes is one of the important representations of membraneless compartmentalization by means of phase transitions of mRNA and corresponding IDPR-containing RNA-binding proteins [27]. The RNAs present in these complexes maintain their solubility [35, 36], which seems to facilitate downstream translation [27].…”

Section: Phase Transitions Of Biomoleculesmentioning

confidence: 99%

“…The RNAs present in these complexes maintain their solubility [35, 36], which seems to facilitate downstream translation [27]. However, phase transitions could occur independently of RNAs only in the presence of proteins, such as in the case of formation of centrosomes (microtubule nucleation sites) [123].…”

Section: Phase Transitions Of Biomoleculesmentioning

confidence: 99%

“…Single-stranded RNA [27, 128] and DNA (ssDNA) [129] are the preferred options for the nucleation of phase transition. Both biomolecules display significantly more plasticity as compared to double-stranded DNA and share such properties as a negative charge and relatively low complexity due to a limited presence of unique building units.…”

Section: Phase Transitions Of Biomoleculesmentioning

confidence: 99%

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At the Interface of Three Nucleic Acids: The Role of RNA-Binding Proteins and Poly(ADP-ribose) in DNA Repair

Alemasova

Lavrik

2017

Acta Naturae

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RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay. When bound to RNA, RBPs act as guardians of the genome integrity at different levels, from DNA damage prevention to the post-transcriptional regulation of gene expression. Recently, RBPs have been shown to participate in DNA repair. This fact is of special interest as DNA repair pathways do not generally involve RNA. DNA damage in higher organisms triggers the formation of the RNA-like polymer – poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA- and RNA-binding proteins to the site of DNA damage. It is suggested that poly(ADP-ribose) and RBPs not only modulate the activities of DNA repair factors, but that they also play an important role in the formation of transient repairosome complexes in the nucleus. Cytoplasmic biomolecules are subjected to similar sorting during the formation of RNA assemblages by functionally related mRNAs and promiscuous RBPs. The Y-box-binding protein 1 (YB-1) is the major component of cytoplasmic RNA granules. Although YB-1 is a classic RNA-binding protein, it is now regarded as a non-canonical factor of DNA repair.

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Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties

Tartwijk

Kaminski

2022

Advanced Biology

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These folds are determined by both protein sequence and solvent properties, and determine protein function. [2] Therefore, the diversity of protein folds in cells allows them to carry out a range of functions, such as catalysis of different reactions. Functional versatility within polypeptide chains is further increased through the presence of multiple independently folding sequences, defined as domains, each associated with distinct functions, such as dimerization or responsiveness to a regulator. However, it is now recognized that some proteins do not have defined conformations, or feature domains that are intrinsically disordered (intrinsically disordered regions, IDRs), and that these confer function by mediating context-dependent proteinprotein interactions. [3] The concept of self-organization of proteins is also applied to assemblies of multiple proteins, in which case it refers to formation of dynamic multi-component structures, [4] including certain oligomeric complexes, filaments, and phase-separated assemblies. In phase-separated assemblies, of which a range exist, IDR-containing proteins form a dense phase within the cytoplasm, commonly referred to as biomolecular condensates. [5] As for folds, the formation of these assemblies depends both on interactions between the phase-separating proteins, which can be mediated by their IDRs, and between these proteins and the surrounding solution. Within the cytoplasm, these phase-separated "droplets" commonly contain RNA, in which case they are referred to as ribonucleoprotein (RNP) granules. They can be considered to have "emergent properties:" certain characteristics can be ascribed to assemblies that are not properties of individual constituent proteins. [6] For instance, biomolecular condensates can display liquid-like properties such as fusion and wetting, which led to their identification as phase-separated droplets. [7] These properties allow them to function as dynamic membraneless organelles, or compartments. This compartmentalization is commonly referred to as occurring on the "mesoscale," which is defined as that range of lengths larger than the size of individual molecular machinery such as ribosomes, but smaller than that of the whole cell. [8] The sensitivity of protein folds and macromolecular interactions to local environmental conditions confers both regulatory potential and risk of loss of function in "extreme" conditions. This regulatory potential is exemplified by and has beenThe cytoplasm is an aqueous, highly crowded solution of active macromolecules. Its properties influence the behavior of proteins, including their folding, motion, and interactions. In particular, proteins in the cytoplasm can interact to form phase-separated assemblies, so-called biomolecular condensates. The interplay between cytoplasmic properties and protein condensation is critical in a number of functional contexts and is the subject of this review. The authors first describe how cytoplasmic properties can affect protein behavior, in particular condensate formation...

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RNA assemblages orchestrate complex cellular processes

Cited by 21 publications

References 85 publications

Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress

At the Interface of Three Nucleic Acids: The Role of RNA-Binding Proteins and Poly(ADP-ribose) in DNA Repair

Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties

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