Restriction lift date: 2028-12-31
Investigating the granule forming properties of SMAUG1 and the consequence of interaction with the 14-3-3 protein family
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Date
2023-03-01
Authors
Fehilly, John Denis
Journal Title
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Publisher
University College Cork
Published Version
Abstract
SMAUG1 is an intrinsically disordered RNA binding protein that forms granules in cells containing RNA. SMAUG1 has been linked to several diseases such as Alzheimers, muscular dystrophy, and cancer. SMAUG1 represents a potentially distinct class of RNA granules and thus is a very interesting target for study. This work furthers our understanding of the SMAUG1 protein by showing that it undergoes rapid recovery following photobleaching indicative of liquid-liquid phase separated granules. Here we also report partial colocalization of SMAUG1 with P-body component Enhancer Of MRNA Decapping 4 (EDC4) and stress granule component Ras GTPase-activating protein-binding protein 1 (G3BP1). Previous work from the Dean lab identified interaction between the 14-3-3 family of proteins and SMAUG1. Here this interaction is validated via co-immunoprecipitation western blot analysis. Further to this potential 14-3-3 binding motifs within SMAUG were mutated and shown to be functional for 14-3-3 binding. Finally, the consequences of 14-3-3 interaction with SMAUG1 granules were assessed. 14-3-3 binding mutant form of SMAUG1 showed a higher propensity for granule formation within cells. Mutant forms of SMAUG1 also showed impaired recovery following photobleaching. This taken together suggests that the 14-3-3 family proteins are negative regulators of SMAUG1 granule formation.
Description
Keywords
RNA , Granules , SMAUG1
Citation
Fehilly, J. D. 2023. Investigating the granule forming properties of SMAUG1 and the consequence of interaction with the 14-3-3 protein family. MRes Thesis, University College Cork.