Fates and functions of <scp>RNA</scp>‐binding proteins under stress

Goswami, Binita; Nag, Sharanya; Ray, Partho Sarothi

doi:10.1002/wrna.1825

Cited by 6 publications

(2 citation statements)

References 179 publications

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“…Previous studies indicate that changes in the RNA-protein interactome can enable cells to respond to both intracellular and extracellular stress ( 12, 13 ) and UV cross-linking, combined with RNA purification and protein identification revealed changes in RNA-protein interactions with heat stress ( 14 ). Therefore, one possible explanation of the interactome changes presented here is that heat stress-induced instability of RNA could mediate a loss of intrinsic RNA-binding specificity and affinity ( 14–17 ) and in doing so, affect the structures of many RBPs as observed here.…”

Section: Discussionmentioning

confidence: 99%

Interactome dynamics during heat stress signal transmission and reception

Park,

Keller,

Kaiser

et al. 2024

Preprint

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Among evolved molecular mechanisms, cellular stress response to altered environmental conditions to promote survival is among the most fundamental. The presence of stress-induced unfolded or misfolded proteins and molecular registration of these events constitute early steps in cellular stress response. However, what stress-induced changes in protein conformations and protein-protein interactions within cells initiate stress response and how these features are recognized by cellular systems are questions that have remained difficult to answer, requiring new approaches. Quantitative in vivo chemical cross-linking coupled with mass spectrometry (qXL-MS) is an emerging technology that provides new insight on protein conformations, protein-protein interactions and how the interactome changes during perturbation within cells, organelles, and even tissues. In this work, qXL-MS and quantitative proteome analyses were applied to identify significant time-dependent interactome changes that occur prior to large-scale proteome abundance remodeling within cells subjected to heat stress. Interactome changes were identified within minutes of applied heat stress, including stress-induced changes in chaperone systems as expected due to altered functional demand. However, global analysis of all interactome changes revealed the largest significant enrichment in the gene ontology molecular function term of RNA binding. This group included more than 100 proteins among multiple components of protein synthesis machinery, including mRNA binding, spliceosomes, and ribosomes. These interactome data provide new conformational insight on the complex relationship that exists between transcription, translation and cellular stress response mechanisms. Moreover, stress-dependent interactome changes suggest that in addition to conformational stabilization of RNA-binding proteins, adaptation of RNA as interacting ligands offers an additional fitness benefit resultant from generally lower RNA thermal stability. As such, RNA ligands also serve as fundamental temperature sensors that signal stress through decreased conformational regulation of their protein partners as was observed in these interactome dynamics.

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Section: Discussionmentioning

confidence: 99%

Interactome dynamics during heat stress signal transmission and reception

Park,

Keller,

Kaiser

et al. 2024

Preprint

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“…RNA-binding proteins (RBPs) are critical mediators of cellular responses, with highly interconnected functions often spanning multiple stages of RNA life cycles (Müller-Mcnicoll and Neugebauer 2013;Goswami et al 2024;Hogan et al 2008). Many RBPs are both complex in sequence-with many functional domains-and pleiotropic in either functions or phenotypes they affect (Hentze et al 2018;Corley et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis

Dutcher,

Gasch

2024

Preprint

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RNA-binding proteins (RBPs) play critical cellular roles by mediating various stages of RNA life cycles. Ssd1, an RBP with pleiotropic effects, has been implicated in aneuploidy tolerance inSaccharomyces cerevisiaebut its mechanistic role remains unclear. Here we used a network-based approach to inform on Ssd1’s role in aneuploidy tolerance, by identifying and experimentally perturbing a network of RBPs that share mRNA targets with Ssd1. We identified RBPs whose bound mRNA targets significantly overlap with Ssd1 targets. For 14 identified RBPs, we then used a genetic approach to generate all combinations of genotypes for euploid and aneuploid yeast with an extra copy of chromosome XII, with and withoutSSD1and/or the RBP of interest. Deletion of 10 RBPs either exacerbated or alleviated the sensitivity of wild-type and/orssd1Δ cells to chromosome XII duplication, in several cases indicating genetic interactions withSSD1in the context of aneuploidy. We integrated these findings with results from a global over-expression screen that identified genes whose duplication complementsssd1Δ aneuploid sensitivity. The resulting network points to a sub-group of proteins with shared roles in translational repression and p-body formation, implicating these functions in aneuploidy tolerance. Our results reveal a role for new RBPs in aneuploidy tolerance and support a model in which Ssd1 mitigates translation-related stresses in aneuploid cells.

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Protein-RNA condensation kinetics via filamentous nanoclusters

Peralta-Martinez,

Visentin,

Salgueiro

et al. 2024

Preprint

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Protein-RNA phase separation is at the center of membraneless biomolecular condensates governing cell physiology and pathology. Using an archetypical viral protein-RNA condensation model, we determined the sequence of events that starts with sub- second formation of a protomer with two RNAs per protein dimer. Association of additional RNA molecules to weaker secondary binding sites in this protomer kickstarts crystallization-like assembly of a molecular condensate. Primary nucleation is faster than the sum of secondary nucleation and growth, which is a multistep process. Protein-RNA nuclei grow over hundreds of seconds into filaments and subsequently into nanoclusters with circa 600 nm diameter. Cryoelectron microscopy reveals an internal structure formed by incoming layers of protein-RNA filaments made of ribonucleoprotein oligomers, reminiscent of genome packing of a nucleocapsid. These nanoclusters progress to liquid condensate droplets that undergo further partial coalescence to yield typical hydrogel-like protein-RNA coacervates that may represent the scaffold of large viral factory condensates in infected cells. Our integrated experimental kinetic investigation exposes rate limiting steps and structures along a key biological multistep pathway present across life kingdoms.

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Fates and functions of RNA‐binding proteins under stress

Cited by 6 publications

References 179 publications

Interactome dynamics during heat stress signal transmission and reception

Interactome dynamics during heat stress signal transmission and reception

Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis

Protein-RNA condensation kinetics via filamentous nanoclusters

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