Elongator complex protein 1 (ELP1) pre-mRNA splicing (ELP1 pre-mRNA splicing)

Elongator complex protein 1 (ELP1) pre-mRNA splicing is a critical therapeutic target for Familial Dysautonomia (FD), a rare neurodegenerative disorder. The disease is primarily caused by a point mutation in the ELP1 gene (formerly known as IKBKAP) that results in the inefficient inclusion of exon 20 during pre-mRNA splicing (Slaugenhaupt et al., 2001, Am J Hum Genet). This splicing defect leads to a tissue-specific reduction of the ELP1 protein, which is a vital component of the Elongator complex responsible for tRNA modifications (Close et al., 2006, Mol Cell). Deficiency in ELP1 disrupts protein translation and leads to the progressive loss of sensory and autonomic neurons (Karlsborn et al., 2014, RNA Biol). Therapeutic approaches aim to correct this defect using small molecules like kinetin or antisense oligonucleotides (ASOs) that promote the inclusion of exon 20 (Sinha et al., 2015, Nucleic Acids Res). By restoring the production of full-length ELP1 protein, these treatments seek to alleviate the symptoms and slow the progression of FD.

Other names

IKBKAP pre-mRNA splicingELP1 exon 20 splicingFamilial dysautonomia splicing defect

Splicing modulation to promote exon 20 inclusion