YTHDF2 destabilizes m 6 A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells.
Autor: | Heck AM; Program in Cell & Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA.; Department of Microbiology, Immunology & Pathology., Russo J; Department of Microbiology, Immunology & Pathology., Wilusz J; Program in Cell & Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA.; Department of Microbiology, Immunology & Pathology., Nishimura EO; Program in Cell & Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA.; Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA., Wilusz CJ; Program in Cell & Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA.; Department of Microbiology, Immunology & Pathology. |
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Jazyk: | angličtina |
Zdroj: | RNA (New York, N.Y.) [RNA] 2020 Jun; Vol. 26 (6), pp. 739-755. Date of Electronic Publication: 2020 Mar 13. |
DOI: | 10.1261/rna.073502.119 |
Abstrakt: | N 6 -methyladenosine (m 6 A) is an abundant post-transcriptional modification that can impact RNA fate via interactions with m 6 A-specific RNA binding proteins. Despite accumulating evidence that m 6 A plays an important role in modulating pluripotency, the influence of m 6 A reader proteins in pluripotency is less clear. Here, we report that YTHDF2, an m 6 A reader associated with mRNA degradation, is highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. Through RNA sequencing, we identified a group of m 6 A-modified transcripts associated with neural development that are directly regulated by YTDHF2. Depletion of YTHDF2 in iPSCs leads to stabilization of these transcripts, loss of pluripotency, and induction of neural-specific gene expression. Collectively, our results suggest YTHDF2 functions to restrain expression of neural-specific mRNAs in iPSCs and facilitate their rapid and coordinated up-regulation during neural induction. These effects are both achieved by destabilization of the targeted transcripts. (© 2020 Heck et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.) |
Databáze: | MEDLINE |
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