An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:4

Enthalten in:

Cell reports methods - 4(2024), 3 vom: 25. März, Seite 100721

Sprache:

Englisch

Beteiligte Personen:

Tang, Yao [VerfasserIn]
Wu, Yifan [VerfasserIn]
Wang, Sainan [VerfasserIn]
Lu, Xiaolan [VerfasserIn]
Gu, Xiangwen [VerfasserIn]
Li, Yong [VerfasserIn]
Yang, Fan [VerfasserIn]
Xu, Ruilin [VerfasserIn]
Wang, Tao [VerfasserIn]
Jiao, Zichen [VerfasserIn]
Wu, Yan [VerfasserIn]
Liu, Liwei [VerfasserIn]
Chen, Jian-Qun [VerfasserIn]
Wang, Qiang [VerfasserIn]
Chen, Qihan [VerfasserIn]

Links:

Volltext

Themen:

2-O-methylation
63231-63-0
Alternative splicing
CP: molecular biology
Diagnose marker
EC 2.1.1.-
Epigenetics
Fibrillarin methyltransferase
Journal Article
MRNA regulation
Methyltransferases
RNA
RNA, Messenger
RNA, Ribosomal
RNA modification
Translation regulation
Virus response

Anmerkungen:

Date Completed 28.03.2024

Date Revised 04.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.crmeth.2024.100721

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369425189