3'-Terminal 2'-O-methylation of lung cancer miR-21-5p enhances its stability and association with Argonaute 2.

Abstract:

:Methylation of miRNAs at the 2'-hydroxyl group on the ribose at 3'-end (2'-O-methylation, 2'Ome) is critical for miRNA function in plants and Drosophila. Whether this methylation phenomenon exists for mammalian miRNA remains unknown. Through LC-MS/MS analysis, we discover that majority of miR-21-5p isolated from human non-small cell lung cancer (NSCLC) tissue possesses 3'-terminal 2'Ome. Predominant 3'-terminal 2'Ome of miR-21-5p in cancer tissue is confirmed by qRT-PCR and northern blot after oxidation/β-elimination procedure. Cancerous and the paired non-cancerous lung tissue miRNAs display different pattern of 3'-terminal 2'Ome. We further identify HENMT1 as the methyltransferase responsible for 3'-terminal 2'Ome of mammalian miRNAs. Compared to non-methylated miR-21-5p, methylated miR-21-5p is more resistant to digestion by 3'→5' exoribonuclease polyribonucleotide nucleotidyltransferase 1 (PNPT1) and has higher affinity to Argonaute-2, which may contribute to its higher stability and stronger inhibition on programmed cell death protein 4 (PDCD4) translation, respectively. Our findings reveal HENMT1-mediated 3'-terminal 2'Ome of mammalian miRNAs and highlight its role in enhancing miRNA's stability and function.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Liang H,Jiao Z,Rong W,Qu S,Liao Z,Sun X,Wei Y,Zhao Q,Wang J,Liu Y,Chen X,Wang T,Zhang CY,Zen K

doi

10.1093/nar/gkaa504

subject

Has Abstract

pub_date

2020-07-27 00:00:00

pages

7027-7040

issue

13

eissn

0305-1048

issn

1362-4962

pii

5857705

journal_volume

48

pub_type

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