CONDBA E210K – UBTF
The UBTF gene encodes a protein that is essential for the transcription of important genes. Transcription is the process where a part of the cellular DNA is copied to an RNA, which then proceeds to the ribosome to produce a protein. One mutation in the UBTF gene, E210K, causes the protein it encodes to become pathologically efficient, resulting in increased activity of RNA polymerase I and higher production of the ribosomal RNA inside the cells [1]. Recent studies have shown that this excess ribosomal RNA production leads to excessive protein production and is destructive to cells, as it results in accumulating damage to the DNA, damage to the ribosomes that produce the cellular proteins, and eventually, cellular death [2].
Only a few studies have explored the progression of CONDBA and attempted to unveil its mechanism(s) of action. These studies include investigating fibroblast cells collected from patients and magnetic resonance imaging (MRI) studies to identify the degeneration process and death of brain cells. While the UBTF mutation is ubiquitously expressed throughout all the cells of the body, the vulnerability of different tissues and systems is not yet fully understood, neither the pattern of progression nor it’s pathophysiology.
References
1.Edvardson, S., et al., Heterozygous de novo UBTF gain-of-function variant is associated with neurodegeneration in childhood. The American Journal of Human Genetics, 2017. 101(2): p. 267-273.
2.Toro, C., et al., A recurrent de novo missense mutation in UBTF causes developmental neuroregression. Human Molecular Genetics, 2018. 27(4): p. 691-705.
3.Wei, T., et al., Small-molecule targeting of RNA polymerase I activates a conserved transcription elongation checkpoint. Cell reports, 2018. 23(2): p. 404-414.
4.Ferreira, R., et al., Targeting the RNA polymerase I transcription for cancer therapy comes of age. Cells, 2020. 9(2): p. 266.
5.Kilanczyk, E., et al., Pharmacological inhibition of spinal cord injury-stimulated ribosomal biogenesis does not affect locomotor outcome. Neuroscience Letters, 2017. 642: p. 153-157.
