Citation: Xue-Jiao You, Lin Li, Tong-Tong Ji, Neng-Bin Xie, Bi-Feng Yuan, Yu-Qi Feng. 6-Thioguanine incorporates into RNA and induces adenosine-to-inosine editing in acute lymphoblastic leukemia cells[J]. Chinese Chemical Letters, ;2023, 34(1): 107181. doi: 10.1016/j.cclet.2022.01.074 shu

6-Thioguanine incorporates into RNA and induces adenosine-to-inosine editing in acute lymphoblastic leukemia cells

Xue-Jiao You ^{a, b} ,
Lin Li ^c ,
Tong-Tong Ji ^a ,
Neng-Bin Xie ^a ,
Bi-Feng Yuan ^{a, b, *,} ,
Yu-Qi Feng ^{a, b}

a.
Department of Chemistry, Sauvage Center for Molecular Sciences, Wuhan University, Wuhan 430072, China
b.
School of Public Health, Wuhan University, Wuhan 430071, China
c.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China

bfyuan@whu.edu.cn

Received Date: 8 December 2021
Revised Date: 4 January 2022
Accepted Date: 26 January 2022
Available Online: 1 February 2022

Figures(4)

6-Thioguanine (6TG) is a widely used chemotherapeutic agent for the treatment of a variety of human diseases including acute lymphoblastic leukemia. After entry into cells, 6TG is metabolically converted into 6-thioguanosine (^SG) nucleotide that can be incorporated into the genome during DNA replication. ^SG in genomic DNA could induce cell death by triggering the post-replicative mismatch repair (MMR) pathway. Meanwhile, incorporation of 6TG into the CpG sites could perturb the global DNA methylation and gene regulation. However, the effect of 6TG on RNA modifications is still unknown. Adenosine-to-inosine (A-to-I) editing in RNA is one of the most common post-transcriptional modifications in mammals and there is growing evidence showing the significant alteration of A-to-I RNA editing in tumor tissues compared to normal tissues. In the current study, we examined the incorporation of 6TG into RNA and investigated its effect on A-to-I editing of bladder cancer-associated protein (BLCAP) transcript in acute lymphoblastic leukemia cells. The results demonstrated that ^SG could be incorporated into various RNA species, with mRNA having the most abundant ^SG. In addition, the results showed 6TG treatment elevated A-to-I editing in BLCAP transcript through upregulating adenosine deaminase 2 acting on RNA (ADAR2), which eventually contributes to the decreased cell viability. This study highlights a new mechanism of the cytotoxicity of 6TG in inducing cell death.
- 6-Thioguanine,
- RNA modification,
- Inosine,
- Leukemia,
- Mass spectrometry
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