Methyl-CpG binding protein 2 pre-messenger RNA (MECP2 pre-mRNA)

Methyl-CpG binding protein 2 (MECP2) pre-messenger RNA is the precursor transcript of the MECP2 gene, which encodes a protein vital for neuronal maturation and the maintenance of synaptic plasticity by binding to methylated DNA and modulating chromatin architecture (UniProt, 2024). Mutations in this transcript, most frequently G-to-A transitions that create premature stop codons or deleterious missense mutations, are the primary cause of Rett syndrome, a progressive X-linked neurodevelopmental disorder (NIH, 2023). The mutant pre-mRNA serves as a therapeutic target for RNA editing technologies that leverage endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes (Sinnamon et al., 2017). By using antisense oligonucleotides, such as ADAR-mediated RNA editing oligonucleotides (AIMers), to guide ADAR to a specific adenosine site, the enzyme catalyzes an Adenosine-to-Inosine (A-to-I) conversion (Wave Life Sciences, 2024). Because the translational machinery interprets Inosine as Guanosine, this process effectively corrects the genetic error at the RNA level, restoring functional MECP2 protein expression while maintaining endogenous regulatory control (Koretskaia et al., 2024). This approach is particularly promising for Rett syndrome because it avoids the risks of protein over-expression associated with traditional gene replacement therapies (Sinnamon et al., 2020).

Other names

Mutant MECP2 pre-mRNA via endogenous ADAR enzymesMECP2 transcriptMethyl-CpG-binding protein 2 RNAMECP2 pre-mRNA

Recruitment of endogenous Adenosine Deaminase Acting on RNA (ADAR) enzymes to catalyze site-specific Adenosine-to-Inosine (A-to-I) editing of mutant pre-mRNA, effectively correcting G-to-A mutations at the RNA level.