The multilayered nucleolus is the primary site of ribosome biogenesis1,2, where successive maturation of small (SSU)3,4 and large (LSU)5 ribosomal subunit precursors occurs. However, the spatiofunctional relationship between pre-rRNA processing and nucleolar substructures and how this adapts to changing cellular physiological demands have remained incompletely understood6,7. Here our spatiotemporal analyses revealed a compartment-specific ribosomal subunit processing in human nucleoli, with SSU processomes maintained in fibrillar centre (FC)-dense fibrillar component (DFC)-periphery dense fibrillar component (PDFC) domains while LSU pre-rRNAs largely transited to PDFC-granular component regions. Slowly proliferating cells exhibited unexpected 5' external transcribed spacer (5' ETS)-centred SSU processing impairment, accompanied by structural remodelling of FC-DFC units and retarded SSU outflux. Direct 5' ETS processing perturbation at least partially recapitulated these FC-DFC unit alterations, supporting the functional interdependence between SSU processing and nucleolar architecture. Notably, anamniote bipartite nucleoli with merged FC-DFC compartments8,9 exhibited distinct 5' ETS distribution and slower pre-rRNA flux compared with multilayered nucleoli in amniotes. Introducing a FC/DFC interface to bipartite nucleoli enhanced processing efficiency, indicating that the evolutionary emergence of nested FC-DFC units may have optimized pre-rRNA processing. Collectively, depicting the spatiotemporal distribution of pre-rRNAs reveals an essential role of 5' ETS-centred processing in maintaining nucleolar substructures and suggests a possible evolutionary advantage of the multilayered structure in amniotes.

The refugee experience is a known risk factor for psychological stress, cardiovascular disease (CVD) and somatic pain. However, the prevalence and comorbidity of these health outcomes in asylum seekers is not elucidated. Here we performed a retrospective, cross-sectional study in which the forensic medical evaluations of 453 globally representative US asylum seekers were analyzed. Outcomes included the prevalence of symptoms of psychological stress, CVD, somatic pain and their comorbidity. Symptoms of psychological stress, CVD and somatic pain were documented in 94%, 47% and 50% of participants, respectively; 46% reported both CVD and stress symptoms, and 31% reported all three. Palpitations, presyncope/syncope, stroke symptoms and chest pain were reported in 33%, 25%, 20% and 16% of individuals with CVD symptoms, respectively. Furthermore, both stress symptoms and pain symptoms were each strongly predictive of comorbid CVD symptoms. These findings indicate that asylum seekers experience a high burden of comorbid and interrelated psychological stress, CVD and somatic pain.