The NIP7 protein is required for accurate pre-rRNA processing in human cells

Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman–Bodian–Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S–80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells

The NIP7 protein is required for accurate pre-rRNA processing in human cells

Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman–Bodian–Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S–80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells

Process evaluation of a primary care based type 2 diabetes remission project in the North East of England.

A type 2 diabetes remission project, Remission in Diabetes (REMI.D), funded by Sport England, was developed by stakeholders based in the North East of England and begun in early 2020. This local delivery pilot sought to tackle health inequalities by working with multiple organisations to demonstrate a way of scaling up an effective type 2 diabetes remission strategy which included both physical activity and dietary components. The intended delivery of the original project was impacted by the COVID-19 pandemic and changes were made to the project delivery in 2022. The aim of this process evaluation was to learn from the reactive decisions taken by stakeholders which altered the REMI.D project in response to the COVID-19 pandemic.Twelve stakeholders (from local authorities, secondary care, universities, NHS England commissioning, Diabetes UK, Sport England, Everyone Active and Active Partnerships) involved in the design and delivery of the intervention took part in a semi-structured interview lasting up to 60 minutes. Interviews were recorded and transcribed verbatim. Thematic analysis used the pre-determined ‘core content’ themes from the Medical Research Council and National Institute for Health Research framework for developing and evaluating complex interventions. Three topics for discussion emerged: a) lack of effective collaboration, b) perception of change, and c) scalability of the intervention. Hierarchy within the stakeholder group initially hampered collaboration. Change was reactive as a result of the COVID-19 pandemic. Project changes reduced project sustainability and scalability but offered valuable learning about the need for explicit project theory for partnership working, co-production with service users, and project flexibility for long-term health behaviour change