Elongator complex protein 1 pre-messenger RNA (ELP1 pre-mRNA)

Elongator complex protein 1 (ELP1) pre-messenger RNA is the primary transcript of the ELP1 gene, which encodes a vital scaffold protein for the Elongator complex. This complex is essential for RNA polymerase II-mediated transcriptional elongation and the chemical modification of wobble-position uridines in tRNAs. In patients with Familial Dysautonomia (FD), a specific point mutation (c.2204+6T>C) in intron 20 of the ELP1 pre-mRNA weakens the 5' splice site, leading to the frequent skipping of exon 20 during RNA processing. This results in a truncated mRNA and a severe deficiency of functional ELP1 protein, particularly in the nervous system, leading to the progressive loss of sensory and autonomic neurons. ELP1 pre-mRNA is a therapeutic target for splicing-modulating small molecules and antisense oligonucleotides (ASOs) that aim to correct this splicing defect. By promoting the inclusion of exon 20, these therapies restore the production of full-length ELP1 protein and potentially halt the progression of the disease.

Other names

IKBKAP pre-mRNAIKAP pre-mRNAElongator complex protein 1 precursor mRNAInhibitor of kappa light polypeptide gene enhancer in B-cells kinase complex-associated protein pre-mRNA

Splicing modulation to promote the inclusion of exon 20 in the mature mRNA transcript by stabilizing the U1 snRNP interaction at the 5' splice site.