Upstream binding transcription factor (UBTF) mRNA (UBTF mRNA)

Upstream binding transcription factor (UBTF) mRNA encodes a nucleolar protein essential for the transcription of ribosomal RNA (rRNA) by RNA polymerase I (UniProt: P17480). It plays a critical role in nucleolar organizer region (NOR) maintenance and ribosome biogenesis, which are vital for cell growth and survival (PubMed: 28625504). A specific recurrent de novo mutation in UBTF (p.Glu210Lys) has been identified as the cause of childhood-onset neurodegeneration with brain atrophy (CONDBA), a progressive disorder characterized by motor and cognitive decline (OMIM: 617491). The disease mechanism is thought to involve a gain-of-function or altered protein activity, making the mRNA an attractive target for knockdown therapies. Antisense oligonucleotides (ASOs), such as ION717, are being developed to target UBTF mRNA for degradation to reduce the levels of the toxic protein (Ionis Pharmaceuticals). This therapeutic approach aims to preserve neurological function by mitigating the cellular stress caused by mutant UBTF. Monitoring treatment efficacy may involve measuring pre-rRNA levels or tracking neuroanatomical changes via MRI. The development of such RNA-targeted therapies represents a significant advancement in treating rare, monogenic neurodegenerative diseases.

Other names

UBF mRNAUpstream binding factor mRNAUBF1 mRNANOR-90 mRNA

Antisense oligonucleotide-mediated mRNA degradation