Ribonucleotide reductase regulatory subunit M2 mRNA (RRM2 mRNA)

Ribonucleotide reductase regulatory subunit M2 (RRM2) mRNA is the transcript encoding the small regulatory subunit of the ribonucleotide reductase (RNR) enzyme complex. RNR is the rate-limiting enzyme responsible for the de novo synthesis of deoxyribonucleoside diphosphates (dNDPs), which are essential precursors for DNA replication and repair (NCBI Gene ID: 6241). RRM2 expression is strictly regulated during the cell cycle, peaking during the S-phase to support DNA synthesis, and its overexpression is a hallmark of many cancers, where it promotes tumor proliferation and genomic instability (UniProt: P15907). Because of its critical role in malignant growth, RRM2 mRNA has been targeted using antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to specifically deplete the RRM2 protein pool. This depletion leads to a shortage of deoxyribonucleotides (dNTPs), resulting in cell cycle arrest and the induction of apoptosis in rapidly dividing cancer cells. Clinical candidates such as GTI-2040 have been investigated in trials for various solid tumors and hematological malignancies, often in combination with traditional chemotherapeutic agents to enhance efficacy and overcome drug resistance (PubMed: 15150581).

Other names

R2 mRNARibonucleoside-diphosphate reductase subunit M2 mRNARR2 mRNARibonucleotide reductase small subunit mRNA

Antisense oligonucleotide or siRNA-mediated degradation of mRNA via RNase H activation or the RNA-induced silencing complex (RISC), leading to reduced RRM2 protein levels and subsequent inhibition of DNA synthesis.