N6-Methyladenosine Modification of LincRNA 1281 is Critically Required for MESC Differentiation Potential

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2018 Mar 13

PMID 29529255

Citations 155

Authors

Dandan Yang

Jing Qiao

Guiying Wang

Yuanyuan Lan

Guoping Li

Xudong Guo

Jiajie Xi

Dan Ye

Songcheng Zhu

Wen Chen

Wenwen Jia

Ye Leng

Xiaoping Wan

Jiuhong Kang

Affiliations

Soon will be listed here.

Abstract

Previous studies have revealed the critical roles of N6-methyladenosine (m6A) modification of mRNA in embryonic stem cells (ESCs), but the biological function of m6A in large intergenic noncoding RNA (lincRNA) is unknown. Here, we showed that the internal m6A modification of linc1281 mediates a competing endogenous RNA (ceRNA) model to regulate mouse ESC (mESC) differentiation. We demonstrated that loss of linc1281 compromises mESC differentiation and that m6A is highly enriched within linc1281 transcripts. Linc1281 with RRACU m6A sequence motifs, but not an m6A-deficient mutant, restored the phenotype in linc1281-depleted mESCs. Mechanistic analyses revealed that linc1281 ensures mESC identity by sequestering pluripotency-related let-7 family microRNAs (miRNAs), and this RNA-RNA interaction is m6A dependent. Collectively, these findings elucidated the functional roles of linc1281 and its m6A modification in mESCs and identified a novel RNA regulatory mechanism, providing a basis for further exploration of broad RNA epigenetic regulatory patterns.

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