Transcription factor UBF depletion in mouse cells results in downregulation of both downstream and upstream elements of the rRNA transcription network

Theophanous, Andria; Christodoulou, Andri; Mattheou, Charalambia; Sibai, Dany S.; Moss, Tom; Santama, Niovi

doi:10.1016/j.jbc.2023.105203

Journal of Biological Chemistry

2023

DOI: 10.1016/j.jbc.2023.105203

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Transcription factor UBF depletion in mouse cells results in downregulation of both downstream and upstream elements of the rRNA transcription network

Andria Theophanous,

Andri Christodoulou,

Charalambia Mattheou

et al.

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2024

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Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis

Chen,

Wu,

Yang

et al. 2024

Preprint

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The nucleolus is the critical non-membranous organelle within nuclei, which responsible for ribosomal DNA (rDNA) transcription and ribosome biogenesis in eukaryotes. The transcription of rDNA, a rate-limiting step for ribosome biogenesis, is tightly regulated to meet the demand for global protein synthesis in response to cell physiology, especially in neurons, which undergo rapid changes in morphology and protein composition during development and synaptic plasticity. However, it is unknown how the pre-initiation complex for rDNA transcription is efficiently assembled within the nucleolus of neurons. Here, we report that the nucleolar protein coronin 2B regulates rDNA transcription and maintains nucleolar function through direct interaction with upstream binding factor (UBF), an activator of RNA polymerase I transcriptional machinery. We show that coronin 2B knockdown impairs the formation of the transcription initiation complex, inhibits rDNA transcription, destroys nucleolar integrity, and ultimately induces nucleolar stress. In turn, coronin 2B-mediated nucleolar stress leads to p53 stabilization and activation, eventually resulting in neuronal apoptosis. Thus, we identified that coronin 2B coordinates with UBF to regulate rDNA transcription and maintain proper nucleolar function in neurons.

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Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis

Chen,

Wu,

Yang

et al. 2024

Preprint

View full text Add to dashboard Cite

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Transcription factor UBF depletion in mouse cells results in downregulation of both downstream and upstream elements of the rRNA transcription network

Cited by 1 publication

References 75 publications

Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis

Coronin 2B deficiency induces nucleolar stress and neuronal apoptosis

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