The GAR domain integrates functions that are necessary for the proper localization of fibrillarin (FBL) inside eukaryotic cells.

Maria Y Shubina,Maria A Tikhomirova,Eugene V Sheval,Eugene A Arifulin,Tatiana Smirnova,Mariya A Sosina,Svyatoslav S Sokolov,Dmitry V Sorokin,Marina V Serebryakova,Yana R Musinova

doi:10.7717/peerj.9029

Abstract

Fibrillarin (FBL) is an essential nucleolar protein that participates in pre-rRNA methylation and processing. The methyltransferase domain of FBL is an example of an extremely well-conserved protein domain in which the amino acid sequence was not substantially modified during the evolution from Archaea to Eukaryota. An additional N-terminal glycine–arginine-rich (GAR) domain is present in the FBL of eukaryotes. Here, we demonstrate that the GAR domain is involved in FBL functioning and integrates the functions of the nuclear localization signal and the nucleolar localization signal (NoLS). The methylation of the arginine residues in the GAR domain is necessary for nuclear import but decreases the efficiency of nucleolar retention via the NoLS. The presented data indicate that the GAR domain can be considered an evolutionary innovation that integrates several functional activities and thereby adapts FBL to the highly compartmentalized content of the eukaryotic cell.

Highlights

Eukaryotic cells contain numerous organelles with or without a membrane(s) that are effectively compartmentalized the cellular processes
We demonstrate that the GAR domain is necessary for FBL functioning and, integrates two activities necessary for proper localization inside eukaryotic cells
Methylation is necessary for nuclear import; one can assume that only functionally active FBL molecules with methylated arginine can be effectively trafficked to the nucleus. (B) FBL accumulates in the granular component (GC) of nucleoli, probably via a charge-dependent mechanism, that is, functions as an nucleolar localization signal (NoLS)

Summary

Introduction

Eukaryotic cells contain numerous organelles with or without a membrane(s) that are effectively compartmentalized the cellular processes. Nuclear proteins are translated in the cytoplasm and, sophisticated mechanisms of nuclear import have evolved. The GAR domain integrates functions that are necessary for the proper localization of fibrillarin (FBL) inside eukaryotic cells. The origin and evolution of the mechanisms that lead to effective compartmentalization of nuclear proteins (i.e., the effective nuclear import and subsequent accumulation inside nuclear bodies) are not obvious. We investigate the possible mechanisms that enabled proteins to adapt to the highly compartmentalized content of eukaryotic cells, focusing on essential nucleolar protein fibrillarin (FBL) as an example

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