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N6-Methyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation.

Abstract：

:N6-Methyladenosine (m6A) RNA modification is present in messenger RNAs (mRNA), ribosomal RNAs (rRNA), and spliceosomal RNAs (snRNA) in humans. Although mRNA m6A modifications have been extensively studied and shown to play critical roles in many cellular processes, the identity of m6A methyltransferases for rRNAs and the function of rRNA m6A modifications are unknown. Here we report a new m6A methyltransferase, ZCCHC4, which primarily methylates human 28S rRNA and also interacts with a subset of mRNAs. ZCCHC4 knockout eliminates m6A4220 modification in 28S rRNA, reduces global translation, and inhibits cell proliferation. We also find that ZCCHC4 protein is overexpressed in hepatocellular carcinoma tumors, and ZCCHC4 knockout significantly reduces tumor size in a xenograft mouse model. Our results highlight the functional significance of an rRNA m6A modification in translation and in tumor biology.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Ma H,Wang X,Cai J,Dai Q,Natchiar SK,Lv R,Chen K,Lu Z,Chen H,Shi YG,Lan F,Fan J,Klaholz BP,Pan T,Shi Y,He C

doi

10.1038/s41589-018-0184-3

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

88-94

issue

1

eissn

1552-4450

issn

1552-4469

pii

10.1038/s41589-018-0184-3

journal_volume

15

pub_type

杂志文章

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