Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the PML Body Biogenesis

Seregey A. Silonov
ORCID logo ,
Yakov I. Mokin
,
Eugene M. Nedelyaev
ORCID logo ,
Eugene Y. Smirnov
,
Irina M. Kuznetsova
ORCID logo ,
Konstantin K. Turoverov
ORCID logo ,
Vladimir N. Uversky
* ORCID logo ,
Alexander V. Fonin
* ORCID logo
Version 1 : Received: 21 October 2023 / Approved: 23 October 2023 / Online: 23 October 2023 (10:49:13 CEST)

A peer-reviewed article of this Preprint also exists.

Silonov, S.A.; Mokin, Y.I.; Nedelyaev, E.M.; Smirnov, E.Y.; Kuznetsova, I.M.; Turoverov, K.K.; Uversky, V.N.; Fonin, A.V. On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies. Biomolecules 2023, 13, 1805. https://doi.org/10.3390/biom13121805 Silonov, S.A.; Mokin, Y.I.; Nedelyaev, E.M.; Smirnov, E.Y.; Kuznetsova, I.M.; Turoverov, K.K.; Uversky, V.N.; Fonin, A.V. On the Prevalence and Roles of Proteins Undergoing Liquid–Liquid Phase Separation in the Biogenesis of PML-Bodies. Biomolecules 2023, 13, 1805. https://doi.org/10.3390/biom13121805

Abstract

The formation and functioning of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, maintenance of genome stability, response to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML-bodies for their tendency to spontaneous liquid-liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs), and remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SOMYylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected.

Keywords

PMLbodies; intrinsically disordered proteins; intrinsically disordered regions; liquidliquid phase separation; membrane-less organelles; protein-protein interactions; posttranslational modifications; SUMOyltion

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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