GTPase HRas messenger RNA (HRAS mRNA)

HRas mRNA is the transcript of the HRAS gene, which encodes a member of the Ras family of small GTPases (NCBI Gene ID: 3265). The resulting HRas protein acts as a critical molecular switch in signal transduction pathways, including the MAPK and PI3K/AKT pathways, which govern cell growth, differentiation, and survival (UniProt P01112). Mutations in HRAS mRNA, particularly at codons 12, 13, or 61, lead to the production of a constitutively active protein that drives oncogenesis in various tissues, such as the bladder, thyroid, and head and neck (PubMed: 15150101). Because the HRas protein has been historically difficult to target with small molecules due to its smooth surface and high affinity for GTP, the mRNA itself has become a therapeutic target. Antisense oligonucleotides (ASOs), such as ISIS 2503, are designed to bind to the HRas mRNA sequence, promoting its degradation via RNase H and thereby preventing the synthesis of the oncogenic protein (PubMed: 11033471). This strategy aims to silence the driver of malignancy at the genetic level, offering a potential treatment for Ras-driven cancers and developmental disorders like Costello syndrome.

Other names

HRAS1 mRNAHarvey rat sarcoma virus oncogene mRNAp21 mRNA transcriptTransforming protein p21 mRNA

Antisense inhibition of translation and RNase H-mediated mRNA degradation