Fragile X messenger ribonucleoprotein 1 mRNA (FMR1 mRNA)

Fragile X messenger ribonucleoprotein 1 (FMR1) mRNA is the transcript of the FMR1 gene, which encodes the FMRP protein, an essential regulator of mRNA transport and translation at neuronal synapses. In healthy individuals, the 5' untranslated region (UTR) of the FMR1 mRNA contains 6 to 54 CGG trinucleotide repeats; however, expansions of these repeats lead to distinct pathological states. In Fragile X-associated tremor/ataxia syndrome (FXTAS), individuals carry a 'premutation' (55-200 repeats) that results in a toxic gain-of-function where elevated levels of FMR1 mRNA form secondary structures, such as hairpins and G-quadruplexes, which sequester vital RNA-binding proteins and undergo repeat-associated non-AUG (RAN) translation. Conversely, in Fragile X syndrome (FXS), a 'full mutation' (>200 repeats) leads to epigenetic silencing of the gene and a total absence of the mRNA and its protein product. Therapeutic strategies targeting FMR1 mRNA primarily focus on FXTAS, utilizing antisense oligonucleotides (ASOs) or small molecules to degrade the transcript or prevent the sequestration of cellular proteins, thereby mitigating neurodegeneration (Source: NIH, PubMed, Ionis Pharmaceuticals).

Other names

Fragile X mental retardation 1 mRNAFMRP mRNAFMR1 transcriptFMR1 messenger RNA

Antisense oligonucleotide-mediated degradation (RNase H-dependent), RNA interference (RNAi), Small molecule inhibition of RNA-protein sequestration, Small molecule disruption of RNA secondary structures (G-quadruplexes/hairpins)