SNURF Inhibitors

The "SNRPN upstream open reading frame" (SNRPN UORF) is a component of the SNRPN (Small Nuclear Ribonucleoprotein Polypeptide N) gene locus, which plays a critical role in the genetic and epigenetic regulation of a cluster of imprinted genes in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13. Not a protein itself, the UORF is a regulatory element located in the 5' untranslated region (5' UTR) upstream of the SNRPN coding sequence.The SNRPN gene is essential for the biogenesis of small nuclear ribonucleoproteins (snRNPs), which are critical components of the spliceosome, the complex responsible for pre-mRNA splicing. The SNRPN UORF plays a regulatory role in the control of SNRPN translation. UORFs are known to be involved in the translational regulation of mRNAs, and their presence can attenuate the translation of the main downstream open reading frame (ORF) by various mechanisms, including ribosome stalling or premature translation termination.

In the context of SNRPN, the UORF is part of a highly complex imprinted domain subject to parental imprinting, a form of epigenetic regulation that results in the gene being expressed exclusively from one parental allele. In the case of SNRPN, it is typically the paternally inherited allele that is active, while the maternal allele is silenced. This imprinting is crucial for normal development, and disruptions in the imprinting process at the SNRPN locus can lead to neurodevelopmental disorders such as Prader-Willi syndrome, which is characterized by intellectual disability, behavioral problems, and obesity, or Angelman syndrome, which includes severe intellectual and developmental disability, seizures, and problems with movement and balance.The SNRPN UORF, by modulating the translation of SNRPN, may indirectly influence the expression of other genes in the PWS/AS region, contributing to the fine-tuned regulatory network that is essential for neurodevelopment and metabolic functions.