| 1 | Cathepsin B S-nitrosylation promotes ADAR1-mediated editing of its own mRNA transcript via an ADD1/MATR3 regulatory axis显示文摘Genetic information is generally transferred from RNA to protein according to the classic“Central Dogma”.Here,we made a striking discovery that post-translational modification of a protein specifically regulates the editing of its own mRNA.We show that S-nitrosylation of cathepsin B(CTSB)exclusively alters the adenosine-to-inosine(A-to-I)editing of its own mRNA.Mechanistically,CTSB S-nitrosylation promotes the dephosphorylation and nuclear translocation of ADD1,leading to the recruitment of MATR3 and ADAR1 to CTSB mRNA.ADAR1-mediated A-to-I RNA editing enables the binding of HuR to CTSB mRNA,resulting in increased CTSB mRNA stability and subsequently higher steady-state levels of CTSB protein.Together,we uncovered a unique feedforward mechanism of protein expression regulation mediated by the ADD1/MATR3/ADAR1 regulatory axis.Our study demonstrates a novel reverse flow of information from the post-translational modification of a protein back to the post-transcriptional regulation of its own mRNA precursor.We coined this process as“Protein-directed EDiting of its Own mRNA by ADAR1(PEDORA)”and suggest that this constitutes an additional layer of protein expression control.“PEDORA”could represent a currently hidden mechanism in eukaryotic gene expression regulation. | Zhe Lin Shuang Zhao Xuesong Li Zian Miao Jiawei Cao Yurong Chen Zhiguang Shi Jia Zhang Dongjin Wang Shaoliang Chen Liansheng Wang Aihua Gu Feng Chen Tao Yang Kangyun Sun Yi Han Liping Xie Hongshan Chen Yong Ji | 2023 | Cell Research2023，33，7： | 0 |
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