Nol9 Is a Spatial Regulator for the Human ITS2 Pre-rRNA Endonuclease-Kinase Complex

Publication date: Available online 6 July 2019Source: Journal of Molecular BiologyAuthor(s): Jacob Gordon, Monica C. Pillon, Robin E. StanleyAbstractThe ribosome plays a universal role in translating the cellular proteome. Defects in the ribosome assembly factor Las1L are associated with congenital lethal motor neuron disease and X-linked intellectual disability disorders, yet its role in processing precursor ribosomal RNA (pre-rRNA) is largely unclear. The Las1L endoribonuclease associates with the Nol9 polynucleotide kinase to form the internal transcribed spacer 2 (ITS2) pre-rRNA endonuclease-kinase machinery. Together, Las1L-Nol9 catalyzes RNA cleavage and phosphorylation to mark the ITS2 for degradation. While ITS2 processing is critical for the production of functional ribosomes, the regulation of mammalian Las1L-Nol9 remains obscure. Here we characterize the human Las1L-Nol9 complex and identify critical molecular features that regulate its assembly and spatial organization. We establish that Las1L and Nol9 form a higher-order complex and identify the regions responsible for orchestrating this intricate architecture. Structural analysis by high-resolution imaging defines the intricate spatial pattern of Las1L-Nol9 within the nucleolar sub-structure linked with late pre-rRNA processing events. Furthermore, we uncover a Nol9 encoded nucleolar localization sequence that is responsible for nucleolar transport of the assembled LasL-Nol9 complex. Together, these data provide...

Source: Journal of Molecular Biology - July 7, 2019 Category: Molecular Biology Source Type: research