RESUMO
Newcastle University UK operates an international campus, NUMed, in Malaysia. NUMed delivers the same medical degree programme as in the UK, within a different cultural context. In this paper, medical education faculty and NUMed graduates with experience working in both the UK and Malaysia provide insights into cross-cultural diversity in approaches to learning. Observations from small and large group teaching and approaches to assessment are discussed in relation to students' cultural backgrounds including previous learning experiences and English language abilities. We provide practice points for educators preparing a diverse range of students to work in global healthcare settings.
RESUMO
The rate of ribosome biogenesis, which is downregulated in terminally differentiated cells and upregulated in most cancers, regulates the growth rate and is linked to the cell's proliferative potential. The U3 box C/D small nucleolar RNP (snoRNP) is an integral component of the small subunit (SSU) processome and is essential for 18S rRNA processing. We show that U3 snoRNP assembly, and therefore U3 snoRNA accumulation, is regulated through the U3-specific protein hU3-55K. Furthermore, we report that the levels of several SSU processome components, including the U3 snoRNA but not other box C/D snoRNAs, are specifically downregulated during human lung (CaCo-2) and colon (CaLu-3) epithelial cell differentiation. c-Myc is reported to play an integral role in regulating ribosome production by controlling the expression of many ribosome biogenesis factors. Our data, however, indicate that this regulation is not dependent on c-Myc since the level of this protein does not change during epithelial cell differentiation. In addition, depletion of c-Myc had only a mild affect on the levels of SSU processome proteins. CaCo-2 cells are colon adenocarcinoma epithelial cells that are believed to revert to their precancerous state during differentiation. This suggests a significant increase in the levels of specific SSU processome components during tumorogenesis.
Assuntos
RNA Nucleolar Pequeno/metabolismo , Ribonucleoproteínas Nucleolares Pequenas/metabolismo , Animais , Sequência de Bases , Células CACO-2 , Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Células HEK293 , Células HeLa , Humanos , Dados de Sequência Molecular , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Conformação de Ácido Nucleico , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Ribossômico 18S/genética , RNA Ribossômico 18S/metabolismo , RNA Nucleolar Pequeno/química , RNA Nucleolar Pequeno/genética , Ribonucleoproteínas Nucleolares Pequenas/genéticaRESUMO
The box C/D small nucleolar RNPs (snoRNPs) are essential for the processing and modification of rRNA. TIP48 and TIP49 are two related AAA(+) proteins that are essential for the formation of box C/D snoRNPs. These proteins are key components of the pre-snoRNP complexes, but their exact role in box C/D snoRNP biogenesis is largely uncharacterized. Here we report that TIP48 and TIP49 interact with one another in vitro, and only the TIP48/TIP49 complex, but not the individual proteins, possesses significant ATPase activity. Loss of TIP48 and TIP49 results in a change in pre-snoRNA levels and a loss of U3 snoRNA signal in the Cajal body. We show that TIP48 and TIP49 make multiple interactions with core snoRNP proteins and biogenesis factors and that these interactions are often regulated by the presence of ATP. Furthermore, we demonstrate that TIP48 and TIP49 efficiently bridge interactions between the core box C/D proteins NOP56 or NOP58 and 15.5K. Our data imply that the snoRNP assembly factor NUFIP can regulate the interactions between TIP48 and TIP49 and the core box C/D proteins. We suggest that snoRNP assembly involves an intricate series of interactions that are mediated/regulated by bridging factors and chaperones.
Assuntos
Proteínas de Transporte/metabolismo , DNA Helicases/metabolismo , Proteínas Nucleares/metabolismo , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Ribonucleoproteínas Nucleolares Pequenas/biossíntese , ATPases Associadas a Diversas Atividades Celulares , Trifosfato de Adenosina/metabolismo , Sequência de Bases , Corpos Enovelados/metabolismo , Células HeLa , Humanos , Hidrólise , Modelos Biológicos , Dados de Sequência Molecular , Mutação/genética , Ligação Proteica , Transporte Proteico , Precursores de RNA/metabolismo , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Ribonucleoproteínas Nucleolares Pequenas/metabolismoRESUMO
The box C/D small nucleolar RNPs (snoRNPs) are essential for the processing and modification of rRNA. The core box C/D proteins are restructured during human U3 box C/D snoRNP biogenesis; however, the molecular basis of this is unclear. Here we show that the U8 snoRNP is also restructured, suggesting that this may occur with all box C/D snoRNPs. We have characterized four novel human biogenesis factors (BCD1, NOP17, NUFIP, and TAF9) which, along with the ATPases TIP48 and TIP49, are likely to be involved in the formation of the pre-snoRNP. We have analyzed the in vitro protein-protein interactions between the assembly factors and core box C/D proteins. Surprisingly, this revealed few interactions between the individual core box C/D proteins. However, the novel biogenesis factors and TIP48 and TIP49 interacted with one or more of the core box C/D proteins, implying that they mediate the assembly of the pre-snoRNP. Consistent with this, we show that NUFIP bridges interactions between the core box C/D proteins in a partially reconstituted pre-snoRNP. Restructuring of the core complex probably reflects the conversion of the pre-snoRNP, where core protein-protein interactions are maintained by the bridging biogenesis factors, to the mature snoRNP.
