Additional sex combs-like 3 (ASXL3) mRNA (ASXL3 mRNA)

Additional sex combs-like 3 (ASXL3) mRNA is the transcript of the ASXL3 gene, which encodes a protein essential for epigenetic regulation and chromatin remodeling (UniProt Q9BZQ8). The ASXL3 protein functions as a scaffold within the Polycomb repressive deubiquitinase (PR-DUB) complex, facilitating the deubiquitination of histone H2A to regulate gene expression (Bainbridge et al., 2013). Mutations in the ASXL3 mRNA, primarily de novo heterozygous nonsense or frameshift mutations, lead to the production of truncated proteins or result in haploinsufficiency, causing Bainbridge-Ropers syndrome (BRS) (OMIM 615114). BRS is a severe neurodevelopmental disorder characterized by intellectual disability, significant speech delays, and distinct craniofacial features (Koboldt et al., 2018). While there are currently no FDA-approved drugs targeting ASXL3 mRNA, it represents a potential target for RNA-based therapeutics such as antisense oligonucleotides (ASOs) or RNA interference (RNAi). These therapeutic strategies aim to either selectively degrade mutant transcripts that may exert dominant-negative effects or utilize splice-modulating ASOs to increase the expression of functional ASXL3 protein from the wild-type allele. Developing such treatments requires a precise understanding of the mRNA's stability and its role in the complex epigenetic landscape of the developing brain.

Other names

ASXL transcriptional regulator 3 mRNAKIAA1350 mRNABainbridge-Ropers syndrome-associated mRNA

Antisense oligonucleotide-mediated transcript degradation or splice modulation