PA01_02 - How ribosomes are made in human cells: structural insights from the nucleus

PA01_02

How ribosomes are made in human cells: structural insights from the nucleus

A. Vanden Broeck^1,*, S. Klinge²

¹University of Liège, Liège, Belgium, ²The Rockefeller University, New York, United States

 

Abstract: During early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes the foundation of essential RNA functional centers and catalyzes the processing of pre-ribosomal RNA by unknown mechanisms.

Here we report a series of 24 cryogenic electron microscopy structures of endogenous human nucleolar and nuclear pre-60S assembly intermediates at resolutions of 2.5-3.0 Angstroms. This unprecedented structural landscape now enables an in-depth mechanistic understanding of the early human large ribosomal subunit assembly. In the nucleolus, the pre-60S structures highlight how protein interaction hubs tether assembly factor complexes to the maturing particles and how GTPases and ATPases, such as DEAD-box RNA helicases, can couple irreversible nucleotide hydrolysis steps to the installation of functional centers. In the nucleus, the progressing pre-60S particles illuminate how the structural plasticity of the pre-rRNA is interrogated by assembly factors and by large multiprotein complexes, such as the rixosome, to coordinate RNA cleavage with RNA exosome-mediated degradation of a pre-rRNA spacer; and how assembly factors interchange is used to drive irreversible fine-tuning of functional centers.

Altogether, our work rationalizes decades of existing data from bacterial and eukaryotic systems, reveals new principles of eukaryotic ribosome assembly and lays the foundation for a mechanistic understanding of human diseases in the context of ribosome assembly.

Disclosure of Interest: None declared