N6-Allyladenosine: A New Small Molecule for RNA Labeling Identified by Mutation Assay

RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report N6-allyladenosine (a6A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a6A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mam...

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Veröffentlicht in:Journal of the American Chemical Society 2017-12, Vol.139 (48), p.17213-17216
Hauptverfasser: Shu, Xiao, Dai, Qing, Wu, Tong, Bothwell, Ian R, Yue, Yanan, Zhang, Zezhou, Cao, Jie, Fei, Qili, Luo, Minkui, He, Chuan, Liu, Jianzhao
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container_end_page 17216
container_issue 48
container_start_page 17213
container_title Journal of the American Chemical Society
container_volume 139
creator Shu, Xiao
Dai, Qing
Wu, Tong
Bothwell, Ian R
Yue, Yanan
Zhang, Zezhou
Cao, Jie
Fei, Qili
Luo, Minkui
He, Chuan
Liu, Jianzhao
description RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report N6-allyladenosine (a6A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a6A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mammalian cells. We also show that human RNA N6-methyladenosine (m6A) methyltransferases METTL3/METTL14 can work with a synthetic cofactor, namely allyl-SAM (S-adenosyl methionine with methyl replaced by allyl) in order to site-specifically install an allyl group to the N6-position of A within specific sequence to generate a6A-labeled RNAs. The iodination of N6-allyl group of a6A under mild buffer conditions spontaneously induces the formation of N1,N6-cyclized adenosine and creates mutations at its opposite site during complementary DNA synthesis of reverse transcription. The existing m6A in RNA is inert to methyltransferase-assisted allyl labeling, which offers a chance to differentiate m6A from A at individual RNA sites. Our work demonstrates a new method for RNA labeling, which could find applications in developing sequencing methods for nascent RNAs and RNA modifications.
doi_str_mv 10.1021/jacs.7b06837
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title N6-Allyladenosine: A New Small Molecule for RNA Labeling Identified by Mutation Assay
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