Journal
NUCLEIC ACIDS RESEARCH
Volume 49, Issue 5, Pages 2403-2417Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab080
Keywords
-
Categories
Funding
- National Health and Medical Research Council of Australia [APP1105801]
- National Health and Medical Research Senior Research Fellowship [FP1079611]
- Monash University
Ask authors/readers for more resources
TIA-1 is an RNA-binding protein that can sequester target RNA into stress granules under stress conditions, with its self-association and liquid-liquid phase separation depend on multiple nucleic acid binding sites. The presence of tandem binding sites is crucial in enhancing phase separation of TIA-1, which is finely tuned by the protein:binding site stoichiometry rather than nucleic acid length. Native tandem TIA-1 binding sites within the 3' UTR of p53 mRNA efficiently enhance phase separation of TIA-1 and may act as potent nucleation sites for stress granule assembly.
TIA-1 is an RNA-binding protein that sequesters target RNA into stress granules under conditions of cellular stress. Promotion of stress granule formation by TIA-1 depends upon self-association of its prion-like domain that facilitates liquid-liquid phase separation and is thought to be enhanced via RNA binding. However, the mechanisms underlying the influence of RNA on TIA-1 self-association have not been previously demonstrated. Here we have investigated the self-associating properties of full-length TIA-1 in the presence of designed and native TIA-1 nucleic acid binding sites in vitro, monitoring phase separation, fibril formation and shape. We show that single stranded RNA and DNA induce liquid-liquid phase separation of TIA-1 in a multisite, sequence-specific manner and also efficiently promote formation of amyloid-like fibrils. Although RNA binding to a single site induces a small conformational change in TIA-1, this alone does not enhance phase separation of TIA-1. Tandem binding sites are required to enhance phase separation of TIA-1 and this is finely tuned by the protein:binding site stoichiometry rather than nucleic acid length. Native tandem TIA-1 binding sites within the 3 ' UTR of p53 mRNA also efficiently enhance phase separation of TIA-1 and thus may potentially act as potent nucleation sites for stress granule assembly.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available