» Articles » PMID: 32384686

Fibrillarin Ribonuclease Activity is Dependent on the GAR Domain and Modulated by Phospholipids

Abstract

Fibrillarin is a highly conserved nucleolar methyltransferase responsible for ribosomal RNA methylation across evolution from Archaea to humans. It has been reported that fibrillarin is involved in the methylation of histone H2A in nucleoli and other processes, including viral progression, cellular stress, nuclear shape, and cell cycle progression. We show that fibrillarin has an additional activity as a ribonuclease. The activity is affected by phosphoinositides and phosphatidic acid and insensitive to ribonuclease inhibitors. Furthermore, the presence of phosphatidic acid releases the fibrillarin-U3 snoRNA complex. We show that the ribonuclease activity localizes to the GAR (glycine/arginine-rich) domain conserved in a small group of RNA interacting proteins. The introduction of the GAR domain occurred in evolution in the transition from archaea to eukaryotic cells. The interaction of this domain with phospholipids may allow a phase separation of this protein in nucleoli.

Citing Articles

Advances in the structure and function of the nucleolar protein fibrillarin.

Zhang X, Li W, Sun S, Liu Y Front Cell Dev Biol. 2024; 12:1494631.

PMID: 39605984 PMC: 11599257. DOI: 10.3389/fcell.2024.1494631.


Phosphorylation of Orc6 During Mitosis Regulates DNA Replication and Ribosome Biogenesis.

Kurniawan F, Chakraborty A, Oishi H, Liu M, Arif M, Chen D Mol Cell Biol. 2024; 44(7):289-301.

PMID: 38867464 PMC: 11253883. DOI: 10.1080/10985549.2024.2356880.


Functional Tuning of Intrinsically Disordered Regions in Human Proteins by Composition Bias.

Kastano K, Mier P, Dosztanyi Z, Promponas V, Andrade-Navarro M Biomolecules. 2022; 12(10).

PMID: 36291695 PMC: 9599065. DOI: 10.3390/biom12101486.


Phase Separation of Intrinsically Disordered Nucleolar Proteins Relate to Localization and Function.

Guillen-Chable F, Bayona A, Rodriguez-Zapata L, Castano E Int J Mol Sci. 2021; 22(23).

PMID: 34884901 PMC: 8657925. DOI: 10.3390/ijms222313095.


Dual-color dSTORM imaging and ThunderSTORM image reconstruction and analysis to study the spatial organization of the nuclear phosphatidylinositol phosphates.

Hoboth P, Sebesta O, Sztacho M, Castano E, Hozak P MethodsX. 2021; 8:101372.

PMID: 34430268 PMC: 8374474. DOI: 10.1016/j.mex.2021.101372.


References
1.
Hamann B, Blind R . Nuclear phosphoinositide regulation of chromatin. J Cell Physiol. 2017; 233(1):107-123. PMC: 7399706. DOI: 10.1002/jcp.25886. View

2.
Tessarz P, Santos-Rosa H, Robson S, Sylvestersen K, Nelson C, Nielsen M . Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification. Nature. 2013; 505(7484):564-8. PMC: 3901671. DOI: 10.1038/nature12819. View

3.
Granneman S, Vogelzangs J, Luhrmann R, van Venrooij W, Pruijn G, Watkins N . Role of pre-rRNA base pairing and 80S complex formation in subnucleolar localization of the U3 snoRNP. Mol Cell Biol. 2004; 24(19):8600-10. PMC: 516741. DOI: 10.1128/MCB.24.19.8600-8610.2004. View

4.
Lapeyre B, Bourbon H, Amalric F . Nucleolin, the major nucleolar protein of growing eukaryotic cells: an unusual protein structure revealed by the nucleotide sequence. Proc Natl Acad Sci U S A. 1987; 84(6):1472-6. PMC: 304456. DOI: 10.1073/pnas.84.6.1472. View

5.
Xing Y, Yao R, Zhang Y, Guo C, Jiang S, Xu G . SLERT Regulates DDX21 Rings Associated with Pol I Transcription. Cell. 2017; 169(4):664-678.e16. DOI: 10.1016/j.cell.2017.04.011. View