PXD028456

PXD028456 is an original dataset announced via ProteomeXchange.

Title	Structural insights into regulatory mechanism of RNA modification by human m6A-METTL associated complex
Description	N6-methyladenosine (m6A) is the most abundant ribonucleotide modification among the eukaryotic messenger RNAs (mRNAs). The m6A “writer” is composed of an m6A-METTL complex (MAC), the catalytic subunit, and an m6A-METTL associated complex (MACOM), the regulatory subunit essential for the enzymatic activity. Here we report the cryo-electron microscopy (cryo-EM) structures of MACOM at 3.0-Å resolution, uncovering that WTAP and VIRMA form the core structure of MACOM and ZC3H13 stretches the conformation by binding VIRMA. The lower 4.4-Å resolution cryo-EM datamap of MACOM in complex with MAC, in combination with crosslinking mass spectrometry and GST-pulldown analysis, elucidates a plausible model of the m6A writer complex, in which MACOM binds MAC mainly through WTAP and METTL3 interaction and both components directly contact with RNA substrates revealed by 4-thiouridine-labeled RNA crosslinking analysis. This work establishes the possible assembly mechanism of MACOM and MAC as an active m6A writer for RNA substrate recognition and modification.
HostingRepository	iProX
AnnounceDate	2022-06-23
AnnouncementXML	Submission_2022-11-24_20:37:05.031.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shichen Su
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-13 23:44:51	ID requested
⏵ 1	2022-11-24 20:37:05	announced

Su S, Li S, Deng T, Gao M, Yin Y, Wu B, Peng C, Liu J, Ma J, Zhang K, A writer complexes. Cell Res, 32(11):982-994(2022) [pubmed]

submitter keyword: RNA m6A modification, m6A writer, m6A-METTL complex (MAC), m6A-METTL associated complex (MACOM), WTAP, VIRMA, ZC3H13, METTL3

Jinbiao Ma
contact affiliation	Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
contact email	majb@fudan.edu.cn
lab head
Shichen Su
contact affiliation	Department of Biochemistry and Biophysics, School of Life Sciences, Fudan University
contact email	scsu15@fudan.edu.cn
dataset submitter

iProX dataset URI