Skip to Content
Merck
  • tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells.

tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells.

PLoS genetics (2014-09-19)
Mayumi Okamoto, Mamoru Fujiwara, Masato Hori, Kaoru Okada, Futoshi Yazama, Hiroaki Konishi, Yegui Xiao, Guangying Qi, Fumio Shimamoto, Takahide Ota, Achim Temme, Masaaki Tatsuka
ABSTRACT

Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay (RTD). The tRNA modifying enzymes, NSUN2 and METTL1, are mammalian orthologs of yeast Trm4 and Trm8, which are required for protecting tRNA against RTD. A simultaneous overexpression of NSUN2 and METTL1 is widely observed among human cancers suggesting that targeting of both proteins provides a novel powerful strategy for cancer chemotherapy. Here, we show that combined knockdown of NSUN2 and METTL1 in HeLa cells drastically potentiate sensitivity of cells to 5-fluorouracil (5-FU) whereas heat stress of cells revealed no effects. Since NSUN2 and METTL1 are phosphorylated by Aurora-B and Akt, respectively, and their tRNA modifying activities are suppressed by phosphorylation, overexpression of constitutively dephosphorylated forms of both methyltransferases is able to suppress 5-FU sensitivity. Thus, NSUN2 and METTL1 are implicated in 5-FU sensitivity in HeLa cells. Interfering with methylation of tRNAs might provide a promising rationale to improve 5-FU chemotherapy of cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fluorouracil, meets USP testing specifications
Pricing and availability is not currently available.
Sigma-Aldrich
5-Fluorouracil, ≥99% (HPLC), powder
Pricing and availability is not currently available.
Sigma-Aldrich
cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis
Pricing and availability is not currently available.
Cisplatin impurity A, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
Supelco
5-Fluorouracil, analytical standard
Pricing and availability is not currently available.
Supelco
Fluorouracil, Pharmaceutical Secondary Standard; Certified Reference Material
Pricing and availability is not currently available.
Fluorouracil, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
USP
Fluorouracil, United States Pharmacopeia (USP) Reference Standard
Pricing and availability is not currently available.
USP
Transplatin, United States Pharmacopeia (USP) Reference Standard
Pricing and availability is not currently available.
Sigma-Aldrich
trans-Platinum(II)diammine dichloride
Pricing and availability is not currently available.
Cisplatin, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Pricing and availability is not currently available.