Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes

The cryo-electron microscopy structures of yeast nucleoplasmic pre-60S ribosomal particles give insight into the function of multiple assembly factors in ribosome biogenesis. Dissecting ribosomal biogenesis in the nucleus The ribosome is one of the largest macromolecular complexes in the eukarotic c...

Full description

Saved in:

Bibliographic Details
Published in:	Nature (London) Vol. 534; no. 7605; pp. 133 - 137
Main Authors:	Wu, Shan, Tutuncuoglu, Beril, Yan, Kaige, Brown, Hailey, Zhang, Yixiao, Tan, Dan, Gamalinda, Michael, Yuan, Yi, Li, Zhifei, Jakovljevic, Jelena, Ma, Chengying, Lei, Jianlin, Dong, Meng-Qiu, Woolford, John L., Gao, Ning
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 02.06.2016 Nature Publishing Group
Subjects:	101/28 101/58 45/70 45/90 631/337/1910 631/337/574/1789 631/45/500 631/535/1258/1259 631/80/389/2052 Active Transport, Cell Nucleus Base Sequence Catalytic Domain Cell Nucleus - chemistry Cell Nucleus - metabolism Cell Nucleus - ultrastructure Cryoelectron Microscopy Cytological research Cytoplasm - metabolism DNA, Ribosomal Spacer - chemistry DNA, Ribosomal Spacer - genetics DNA, Ribosomal Spacer - metabolism DNA, Ribosomal Spacer - ultrastructure Genetic research GTP Phosphohydrolases - chemistry GTP Phosphohydrolases - metabolism GTP Phosphohydrolases - ultrastructure GTP-Binding Proteins - chemistry GTP-Binding Proteins - metabolism GTP-Binding Proteins - ultrastructure Humanities and Social Sciences letter Models, Molecular Molecular Sequence Data Molecular structure multidisciplinary Nuclear Proteins - chemistry Nuclear Proteins - metabolism Nuclear Proteins - ultrastructure Nucleolus organizer region Polypeptides Protein Binding Protein research Protein synthesis Proteins Ribonucleic acid Ribonucleoproteins - chemistry Ribonucleoproteins - metabolism Ribonucleoproteins - ultrastructure Ribosomal Proteins - chemistry Ribosomal Proteins - isolation & purification Ribosomal Proteins - metabolism Ribosomal Proteins - ultrastructure Ribosome Subunits, Large, Eukaryotic - chemistry Ribosome Subunits, Large, Eukaryotic - metabolism Ribosome Subunits, Large, Eukaryotic - ultrastructure Ribosomes RNA RNA, Fungal - genetics RNA, Fungal - metabolism RNA, Fungal - ultrastructure RNA, Ribosomal - genetics RNA, Ribosomal - metabolism RNA, Ribosomal - ultrastructure Rotation Saccharomyces cerevisiae - chemistry Saccharomyces cerevisiae - cytology Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae - ultrastructure Saccharomyces cerevisiae Proteins - chemistry Saccharomyces cerevisiae Proteins - isolation & purification Saccharomyces cerevisiae Proteins - metabolism Saccharomyces cerevisiae Proteins - ultrastructure Science Yeasts United States China
ISSN:	0028-0836, 1476-4687
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The cryo-electron microscopy structures of yeast nucleoplasmic pre-60S ribosomal particles give insight into the function of multiple assembly factors in ribosome biogenesis. Dissecting ribosomal biogenesis in the nucleus The ribosome is one of the largest macromolecular complexes in the eukarotic cell and its biogenesis is a highly complex process, involving hundreds of assembly factors, including many GTPases, ATPases and kinases. To gain insight into the function of these factors, Ning Gao and colleagues used cryo-electron microscopy to characterize structures of several nuclear pre-60S particles. Their data localize more than twenty assembly factors, which are particularly concentrated in two regions. The series of structures outlines three remodelling events that occur to the particle before it is transported to the cytoplasm. Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm 1 , 2 . Hundreds of assembly factors, organized into sequential functional groups 3 , 4 , facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo-electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-0836 1476-4687
DOI:	10.1038/nature17942