Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs

被引：48

作者：

Liao, Han ^{[1
]}

Gaur, Anushri ^{[1
]}

McConie, Hunter ^{[1
]}

Shekar, Amirtha ^{[1
]}

Wang, Karen ^{[2
]}

Chang, Jeffrey T. ^{[1
]}

Breton, Ghislain ^{[1
]}

Denicourt, Catherine ^{[1
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA

[2] Rice Univ, Wiess Coll, Houston, TX 77251 USA

来源：

NUCLEIC ACIDS RESEARCH | 2022年 / 50卷 / 18期

基金：

美国国家卫生研究院;

关键词：

NUCLEOLAR PROTEIN P120; CELL-CYCLE; RNA METHYLTRANSFERASE; ANTIGEN P120; EXPRESSION; P53; PROLIFERATION; METHYLATION; REVEALS; U8;

D O I：

10.1093/nar/gkac817

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

5-Methylcytosine (m(5)C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m(5)C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m(5)C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the deposition of m(5)C at position 4447 on the 28S rRNA. We also find that NOP2/NSUN1 binds to the 5 ' ETS region of the pre-rRNA transcript and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. We provide evidence that NOP2/NSUN1 facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. Remarkably, expression of both WT and catalytically inactive NOP2/NSUN1 in knockdown background rescues the rRNA processing defects and the stable assembly of box C/D snoRNP complexes, suggesting that NOP2/NSUN1-mediated deposition of m(5)C on rRNA is not required for ribosome synthesis.

引用

页码：10695 / 10716

页数：22