Proteomic analysis reveals the recruitment of intrinsically disordered regions to stress granules

Abstract

1The authors provide an in-depth proteomic study of yeast heat stress granule (SG) proteins. They 2 identified intrinsic disordered regions (IDRs) as one of the main features shared by these proteins and 3 demonstrated IDRs can be sufficient for SG recruitment. 4 3 Abstract 1Heat-stress triggers the formation of condensates known as stress granules (SGs), which store non-2 translating mRNA and stalled translation initiation complexes. To gain a better understanding of SGs, we 3 identified yeast proteins that sediment after heat-shock by mass spectrometry. Heat-regulated proteins 4 are biased toward a subset of abundant proteins that are significantly enriched in intrinsically disordered 5 regions (IDRs). SG localization of over 80 heat-regulated proteins was confirmed using microscopy, 6 including 32 proteins that were not known previously to localize to SGs. We find that several IDRs are 7 sufficient to mediate SG recruitment. Moreover, the diffusive exchange of IDRs within SGs, observed via 8 FRAP, can be highly dynamic while other components remain immobile. Lastly, we showed that the IDR 9 of the Ubp3 deubiquitinase is critical for SG formation. This work confirms that IDRs play an important 10 role in cellular compartmentalization upon stress, can be sufficient for SG incorporation, can remain 11 dynamic in vitrified SGs, and play a vital role during heat-stress. 12

Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granules

“…S7B). Likewise, IDRs are enriched among proteins that are recruited to heat-induced stress granules in yeast (44); however, while almost every PrLD in our dataset contains regions that are predicted to be disordered by multiple prediction methods [IUPred (45), FoldUnfold (46), and FoldIndex (47)], the PrLDs that failed to assemble in response to heat stress actually tended to show a higher degree of predicted disorder (SI Appendix, Fig. S8).…”

Chandipura Virus Forms Cytoplasmic Inclusion Bodies through Phase Separation and Proviral Association of Cellular Protein Kinase R and Stress Granule Protein TIA-1

“…Numerous reports recently came out to suggest viral proteomes contain intrinsically disordered proteins (IDPs) and IDP regions (IDPRs), which are proteins or protein regions that lack unique (or ordered) three-dimensional structures [5,64,65]. Of late, a number of reports also suggested involvement of IDPs and IDPRs in cell signaling [66], assembly of cellular SGs [67,68] and condensation and aggregation of viral and cellular proteins to form IBs [69]. In this direction, we published a report emphasizing the varying degrees of disorder in all five CHPV proteins, with the maximum level of intrinsic disorder propensity found in phosphoprotein (P) [5].…”