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

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

doi:10.7717/peerj.9029

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

PeerJ. 2020 Apr 28:8:e9029. doi: 10.7717/peerj.9029. eCollection 2020.

Authors

Affiliations

¹ Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
² Laboratory of Mathematical Methods of Image Processing, Faculty of Computational Mathematics and Cybernetics, Lomonosov Moscow State University, Moscow, Russia.
³ Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
⁴ Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
⁵ Department of Cell Biology and Histology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
⁶ Skobelkin State Scientific Center of Laser Medicine FMBA, Moscow, Russia.
⁷ LIA 1066 LFR2O French-Russian Joint Cancer Research Laboratory, Villejuif, France.

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.

Keywords: Fibrillarin (FBL); GAR domain; Methylation; NLS; NoLS; Nucleolus; Nucleus.

Grants and funding

The work was supported by the Russian Science Foundation (grant 17-75-20199 to Yana R. Musinova) and President’s grant for young scientists (grant МК-716.2018.4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.