RESUMO
The reciprocal relationship between education and health is well-established, emphasizing the need for integrating health, nutrition, and well-being components into educational sector planning. Despite widespread acknowledgment of this need, countries lack concrete measures to achieve this integration. We examine challenges that countries have faced and the progress they have made in integrating these components into education sector plans and review the extent to which existing educational planning guidelines and tools address health and well-being. The review reveals a significant underrepresentation of health, well-being, and related themes in existing educational planning frameworks. Recent tools and frameworks developed to support a more holistic approach to education have not yet been widely adopted in standard education sector planning processes. The implementation of such approaches remains inconsistent, with significant barriers including limited cross-sectoral collaboration, lack of capacity, and insufficient funding, among others. Addressing these gaps requires improved guidance, technical support, and a multisectoral approach to education planning that includes health, nutrition, and well-being as fundamental components of foundational learning, supported by political commitment, capacity, and adequate financing.
Assuntos
Países em Desenvolvimento , Humanos , Educação , Cooperação InternacionalRESUMO
The coordination of RNA polymerase I transcription with pre-rRNA processing, preribosomal particle assembly, and nuclear export is a finely tuned process requiring the concerted actions of a number of accessory factors. However, the exact functions of some of these proteins and how they assemble in subcomplexes remain poorly defined. LAS1L was first described as a nucleolar protein required for maturation of the 60S preribosomal subunit. In this paper, we demonstrate that LAS1L interacts with PELP1, TEX10, and WDR18, the mammalian homologues of the budding yeast Rix1 complex, along with NOL9 and SENP3, to form a novel nucleolar complex that cofractionates with the 60S preribosomal subunit. Depletion of LAS1L-associated proteins results in a p53-dependent G1 arrest and leads to defects in processing of the pre-rRNA internal transcribed spacer 2 region. We further show that the nucleolar localization of this complex requires active RNA polymerase I transcription and the small ubiquitin-like modifier-specific protease SENP3. Taken together, our data identify a novel mammalian complex required for 60S ribosomal subunit synthesis, providing further insight into the intricate, yet poorly described, process of ribosome biogenesis in higher eukaryotes.
Assuntos
Proteínas Nucleares/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Nucléolo Celular/metabolismo , Proteínas Correpressoras/metabolismo , Cisteína Endopeptidases/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Células HCT116 , Células HEK293 , Humanos , Proteínas Nucleares/genética , Polinucleotídeo 5'-Hidroxiquinase/metabolismo , Sumoilação , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal particles, which transiently associate with numerous nonribosomal factors before mature 60S and 40S subunits are formed and exported in the cytoplasm, are generated. Here we identify Las1L as a previously uncharacterized nucleolar protein required for ribosome biogenesis. Depletion of Las1L causes inhibition of cell proliferation characterized by a G1 arrest dependent on the tumor suppressor p53. Moreover, we demonstrate that Las1L is crucial for ribosome biogenesis and that depletion of Las1L leads to inhibition of rRNA processing and failure to synthesize the mature 28S rRNA. Taken together, our data demonstrate that Las1L is essential for cell proliferation and biogenesis of the 60S ribosomal subunit.