A key nucleolar protein, fibrillarin, has emerged as an important pharmacological target as its aberrant expression and localization are related to tumorigenesis, chemoresistance and poor survival in breast cancer patients. Fibrillarin contains a N-terminal low complexity sequence (LC) domain with a skewed amino acid distribution, which is known to undergo a phase transition to liquid-like droplets. However, the underlying mechanism of the phase transition of the fibrillarin LC domain and its physiological function are still elusive. In this study, we show that the localization of fibrillarin and its association with RNA binding proteins is regulated by this phase transition. Phenylalanine-to-serine substitutions of the phenylalanine:glycine repeats in the fibrillarin LC domain impede its phase transition into liquid-like droplets, as well as the hydrogel-like state composed of polymers, and also its incorporation into hydrogel or liquid-like droplets composed of wild-type LC domains. When expressed in cultured cells, fibrillarin containing the mutant LC domain fails to localize to the dense fibrillar component of nucleoli in the same way as intact fibrillarin. Moreover, the phase transition of the fibrillarin LC domain is required for the interaction of fibrillarin with other RNA binding proteins, such as FUS, TAF15, DDX5 and DHX9. Taken together, the results suggest that the phenylalanine residues in the LC domain are critical for the phase transition of fibrillarin, which in turn regulates the sub-nucleolar localization of fibrillarin and its interaction with RNA binding proteins, providing a useful framework for regulating the function of fibrillarin.
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In the brain, cocaine exposure results in mitochondrial DNA damage, depletion of ATP and increased oxidative stress, coupled with increased mitochondrial fission. Therapies preventing such bioenergetic impairment may hold promise in mitigating cocaine pathology and addiction. You can read more about this in the review by Thornton and colleagues (pp. 749–764) in this issue. Image provided by Claire Thornton.
Research Article|
February 24 2021
Phase transition of fibrillarin LC domain regulates localization and protein interaction of fibrillarin
Eunji Kim;
Eunji Kim
Investigation
Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea
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Ilmin Kwon
Conceptualization, Supervision, Writing - original draft, Project administration, Writing - review & editing
Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea
Correspondence: Ilmin Kwon (ilmin.kwon@skku.edu)
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Publisher: Portland Press Ltd
Received:
November 02 2020
Revision Received:
January 25 2021
Accepted:
February 01 2021
Accepted Manuscript online:
February 01 2021
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2021
Biochem J (2021) 478 (4): 799–810.
Article history
Received:
November 02 2020
Revision Received:
January 25 2021
Accepted:
February 01 2021
Accepted Manuscript online:
February 01 2021
Citation
Eunji Kim, Ilmin Kwon; Phase transition of fibrillarin LC domain regulates localization and protein interaction of fibrillarin. Biochem J 26 February 2021; 478 (4): 799–810. doi: https://doi.org/10.1042/BCJ20200847
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