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DNA-guided Photoactivatable Probe-based Chemical Proteomics Reveals the Reader Protein of mRNA Methylation

ABSTRACT: We report a DNA templated chemistry and photo-crosslinking based method to detect the readers of mRNA modification. By use of N6-methyladenosine (m6A), we illustrated that this method can be successfully utilized for labelling and enriching the readers of mRNA modification, as well as for the discovery of new partners. Thus we applied this strategy to a new modification 2'-O-methyladenosine. As a result, DDX1 was identified and verified as a potential reader by in vitro and in vivo experiments. Our study therefore provides a powerful chemical proteomics tool for identifying the readers of mRNA modification and reveals the underlying function of mRNA modification.

ORGANISM(S): Homo Sapiens

SUBMITTER: Kai Zhang

PROVIDER: PXD019480 | iProX | Sat May 30 00:00:00 BST 2020

REPOSITORIES: iProX

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DNA-guided photoactivatable probe-based chemical proteomics reveals the reader protein of mRNA methylation.

Huang Yepei Y Bai Xue X Guo Zhenchang Z Dong Hanyang H Fu Yun Y Zhang Hui H Zhai Guijin G Tian Shanshan S Wang Ye Y Zhang Kai K

iScience 20210828 9

Chemical modification on mRNA can recruit specific binding proteins (readers/partners) to determine post-transcriptional gene regulation. However, the identification of the reader is extremely limited owing to the rather weak and highly dynamic non-covalent interactions between mRNA modification and reader, and therefore the sensitive and robust approaches are desirable. Here, we report a DNA-guided photoactivatable-based chemical proteomic approach for profiling the readers of mRNA methylation. ...[more]

PMID: 34553132

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