一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Nucleic Acids Research >>article
Nucleic Acids Research

Nucleic Acids Research

IF: 16.6
Download PDF

Fluoropyrimidines trigger decay of hypomodified tRNA in yeast.

Published:10 June 2024 DOI: 10.1093/nar/gkae341 PMID: 38716877
Katharina G?rlitz,?Larissa Bessler,?Mark Helm,?Raffael Schaffrath,?Roland Klassen

Abstract

Therapeutic fluoropyrimidines 5-fluorouracil (5-FU) and 5-fluorocytosine (5-FC) are in long use for treatment of human cancers and severe invasive fungal infections, respectively. 5-Fluorouridine triphosphate represents a bioactive metabolite of both drugs and is incorporated into target cells' RNA. Here we use the model fungus Saccharomyces cerevisiae to define fluorinated tRNA as a key mediator of 5-FU and 5-FC cytotoxicity when specific tRNA methylations are absent. tRNA methylation deficiency caused by loss of Trm4 and Trm8 was previously shown to trigger an RNA quality control mechanism resulting in partial destabilization of hypomodified tRNAValAAC. We demonstrate that, following incorporation into tRNA, fluoropyrimidines strongly enhance degradation of yeast tRNAValAAC lacking Trm4 and Trm8 dependent methylations. At elevated temperature, such effect occurs already in absence of Trm8 alone. Genetic approaches and quantification of tRNA modification levels reveal that enhanced fluoropyrimidine cytotoxicity results from additional, drug induced uridine modification loss and activation of tRNAValAAC decay involving the exonuclease Xrn1. These results suggest that inhibition of tRNA methylation may be exploited to boost therapeutic efficiency of 5-FU and 5-FC.

Substances (3)

Related products
Procduct Name CAS Molecular Formula Supplier Price
5-Fluorouracil 51-21-8 C4H3FN2O2 1107 suppliers $5.00-$3543.55
5-Fluorocytosine 2022-85-7 C4H4FN3O 946 suppliers $3.00-$1500.00
5-FLUOROURIDINE 5-Fluorouridine 4 suppliers Inquiry

Similar articles

IF:4.1

High-level living cell production of cytidine-5′-diphosphocholine in metabolically engineered yeast

Journal of biotechnology Yanna Ren , Qi Liu ,etc Published: 20 November 2021
IF:0

Potassium bicarbonate reduces postharvest decay development on bell pepper fruits

Journal of Horticultural Science E. Fallik,?S. Grinberg,etc Published: 1 January 1997
IF:4.8

Advances in autophagy modulation of natural products in cervical cancer

Journal of ethnopharmacology Tao Tao , Ping Zhang ,etc Published: 5 October 2023
凤冈县| 尉氏县| 桂平市| 揭西县| 攀枝花市| 准格尔旗| 高尔夫| 阿拉善盟| 灵川县| 曲阳县| 玛纳斯县| 驻马店市| 华池县| 汤原县| 三都| 霍城县| 巴林右旗| 上杭县| 全州县| 无极县| 九江市| 海南省| 邢台市| 福州市| 沙湾县| 万年县| 南阳市| 怀来县| 盘山县| 左权县| 长岭县| 南江县| 雅江县| 太仆寺旗| 闸北区| 德安县| 太和县| 星子县| 敦化市| 蕲春县| 洞口县|