High-Resolution Mapping Reveals a Conserved, Widespread, Dynamic mRNA Methylation Program in Yeast Meiosis

被引：518

作者：

Schwartz, Schraga ^{[1
]}

Agarwala, Sudeep D. ^{[2
]}

Mumbach, Maxwell R. ^{[1
]}

Jovanovic, Marko ^{[1
]}

Mertins, Philipp ^{[1
]}

Shishkin, Alexander ^{[1
]}

Tabach, Yuval ^{[3
,4
]}

Mikkelsen, Tarjei S. ^{[1
]}

Satija, Rahul ^{[1
]}

Ruvkun, Gary ^{[3
,4
]}

Carr, Steven A. ^{[1
]}

Lander, Eric S. ^{[1
,5
,6
]}

Fink, Gerald R. ^{[1
,2
]}

Regev, Aviv ^{[1
,7
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[5] MIT, Dept Biol, Cambridge, MA 02139 USA

[6] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA

[7] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA

来源：

CELL | 2013年 / 155卷 / 06期

基金：

美国国家卫生研究院;

关键词：

SACCHAROMYCES-CEREVISIAE; NUCLEAR-RNA; N-6-METHYLADENOSINE; TRANSCRIPTION; IME4; DIVERGENCE; M(6)A-SEQ; SEQUENCES; RESIDUES; PATHWAY;

D O I：

10.1016/j.cell.2013.10.047

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：

N-6-methyladenosine (m(6)A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m(6)A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated eight out of eight methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time course and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminate a conserved, dynamically regulated methylation program in yeast meiosis and provide an important resource for studying the function of this epitranscriptomic modification.

引用

页码：1409 / 1421

页数：13

共 35 条

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