Principles of human pre-60 S biogenesis

Abstract

During the early stages of human large ribosomal subunit (60 S ) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60 S particles by an unknown mechanism. Here, we report a series of cryo–electron microscopy structures of human nucleolar and nuclear pre-60 S assembly intermediates at resolutions of 2.5 to 3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how guanosine triphosphatases and adenosine triphosphatase couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA-processing complex, the rixosome, couples large-scale RNA conformational changes with pre–ribosomal RNA processing by the RNA degradation machinery. Our ensemble of human pre-60 S particles provides a rich foundation with which to elucidate the molecular principles of ribosome formation.

Pre-ribosomal particles from nucleoli to cytoplasm

“…To complete them, a number of nuclear assembly factors are required. For example, an important transition of pre-60S nuclear maturation is the rotation of the 5S RNP sub-complex, and only after this rotation the further processing leads to the mature 5.8S rRNA [ 9 ]. Nucleoli are formed by liquid-liquid phase separation in response to ongoing rRNA transcription [ 5 , 10 , 11 ].…”