TY - JOUR

T1 - High-resolution structure of eukaryotic Fibrillarin interacting with Nop56 amino-terminal domain

AU - Höfler, Simone

AU - Lukat, Peer

AU - Blankenfeldt, Wulf

AU - Carlomagno, Teresa

N1 - Funding Information: We thank DESY (Hamburg, Germany), a member of the Helmholtz Association HGF, for the provision of experimental facilities. Parts of this research were carried out at PETRA III using beamline P11. The authors thank Ute Widow and Susanne zur Lage, HZI, for excellent technical assistance in the wet lab. This work has been funded by the Deutsche Forschungsgemeinschaft through a project grant to T.C. in the frame of the SPP “Chemical Biology of Natural Nucleic Acids Modifications” (CA 294/11-1).

PY - 2021/4

Y1 - 2021/4

N2 - Ribosomal RNA (rRNA) carries extensive 2′′-O-methyl marks at functionally important sites. This simple chemical modification is thought to confer stability, promote RNA folding, and contribute to generate a heterogenous ribosome population with a yet-uncharacterized function. 2′′-O-methylation occurs both in archaea and eukaryotes and is accomplished by the Box C/D RNP enzyme in an RNA-guided manner. Extensive and partially conflicting structural information exists for the archaeal enzyme, while no structural data is available for the eukaryotic enzyme. The yeast Box C/D RNP consists of a guide RNA, the RNA-primary binding protein Snu13, the two scaffold proteins Nop56 and Nop58, and the enzymatic module Nop1. Here we present the high-resolution structure of the eukaryotic Box C/D methyltransferase Nop1 from Saccharomyces cerevisiae bound to the amino-terminal domain of Nop56. We discuss similarities and differences between the interaction modes of the two proteins in archaea and eukaryotes and demonstrate that eukaryotic Nop56 recruits the methyltransferase to the Box C/D RNP through a protein-protein interface that differs substantially from the archaeal orthologs. This study represents a first achievement in understanding the evolution of the structure and function of these proteins from archaea to eukaryotes.

AB - Ribosomal RNA (rRNA) carries extensive 2′′-O-methyl marks at functionally important sites. This simple chemical modification is thought to confer stability, promote RNA folding, and contribute to generate a heterogenous ribosome population with a yet-uncharacterized function. 2′′-O-methylation occurs both in archaea and eukaryotes and is accomplished by the Box C/D RNP enzyme in an RNA-guided manner. Extensive and partially conflicting structural information exists for the archaeal enzyme, while no structural data is available for the eukaryotic enzyme. The yeast Box C/D RNP consists of a guide RNA, the RNA-primary binding protein Snu13, the two scaffold proteins Nop56 and Nop58, and the enzymatic module Nop1. Here we present the high-resolution structure of the eukaryotic Box C/D methyltransferase Nop1 from Saccharomyces cerevisiae bound to the amino-terminal domain of Nop56. We discuss similarities and differences between the interaction modes of the two proteins in archaea and eukaryotes and demonstrate that eukaryotic Nop56 recruits the methyltransferase to the Box C/D RNP through a protein-protein interface that differs substantially from the archaeal orthologs. This study represents a first achievement in understanding the evolution of the structure and function of these proteins from archaea to eukaryotes.

KW - 2′′-O-methylation

KW - Eukaryotic Box C/D RNP

KW - Fibrillarin

KW - Nop56

KW - Protein-protein complex structure

UR - http://www.scopus.com/inward/record.url?scp=85103057891&partnerID=8YFLogxK

U2 - 10.1261/rna.077396.120

DO - 10.1261/rna.077396.120

M3 - Article

C2 - 33483369

AN - SCOPUS:85103057891

VL - 27

SP - 496

EP - 512

JO - RNA

JF - RNA

SN - 1355-8382

IS - 4

ER -