Fionna E Loughlin, Danella L West, Menachem J Gunzburg, Saboora Waris, Simon A Crawford, Matthew C J Wilce, and Jacqueline A Wilce
Nucleic Acids Research, Volume 49, Issue 5, 18 March 2021, Pages 2403–2417, https://doi.org/10.1093/nar/gkab080
Phase separation (PS) drives subcellular compartmentalization that underlies the formation of non-membrane bound RNA-protein granules such as stress granules. Disturbance in stress granule dynamics is thought to drive pathological inclusions in several neurodegenerative diseases. Understanding the processes underlying PS of protein/RNA complexes and their progression to pathological aggregate will help understand disease progression. Here the authors measured the RNA induced PS of full length TIA-1 protein and the formation of amyloid-like fibres. They determined that while a single site oligonucleotide induced conformational change, tandem sites were required and sufficient to promote PS. The PS was finely tuned according to protein:RNA binding site stoichiometry rather than RNA length. Tandem TIA-1 binding sites within native target 3’UTR RNA promoted TIA-1 PS. The study provides insight into the way stress granule formation may be initiated and modulated by TIA-1/RNA interactions.