Dataset Information

YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m⁶A/mRNA pathway.

ABSTRACT: As the foundation of male fertility, spermatogenesis is a complicated and highly controlled process. YTHDF2 plays regulatory roles in biological processes through accelerating the degradation of target mRNAs. However, the function of YTHDF2 in spermatogenesis remains elusive. Here, we knocked out Ythdf2 in mouse spermatogonia via CRISPR/Cas9, and found that depletion of Ythdf2 mainly downregulated the expression of matrix metallopeptidase (MMPs), thus affecting cell adhesion and proliferation. m⁶A-IP-PCR and RIP-PCR analysis showed that Mmp3, Mmp13, Adamts1 and Adamts9 were modified with m⁶A and simultaneously interacted with YTHDF2. Moreover, inhibition of Mmp13 partially rescued the phenotypes in Ythdf2-KO cells. Taken together, YTHDF2 regulates cell-matrix adhesion and proliferation through modulating the expression of Mmps by the m⁶A/mRNA degradation pathway.

SUBMITTER: Huang T

PROVIDER: S-EPMC6971064 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m<sup>6</sup>A/mRNA pathway.

Huang Tao T Liu Zidong Z Zheng Yi Y Feng Tongying T Gao Qiang Q Zeng Wenxian W

Cell death & disease 20200120 1

As the foundation of male fertility, spermatogenesis is a complicated and highly controlled process. YTHDF2 plays regulatory roles in biological processes through accelerating the degradation of target mRNAs. However, the function of YTHDF2 in spermatogenesis remains elusive. Here, we knocked out Ythdf2 in mouse spermatogonia via CRISPR/Cas9, and found that depletion of Ythdf2 mainly downregulated the expression of matrix metallopeptidase (MMPs), thus affecting cell adhesion and proliferation. m ...[more]

PMID: 31959747

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Project description:BackgroundPathological cardiac hypertrophy is a major contributor of heart failure (HF), which seriously threatens human's health world widely. Deregulation of m6A RNA methylation, and m6A methyltransferases and de-methyltransferases have been demonstrated to act essential roles in cardiac hypertrophy and HF. Here, we studied the potential roles and its underlying mechanisms of m6A Reader YTHDF proteins in HF. In this study, we constructed HF mouse model by transverse aortic constriction surgery. Primary cardiomyocytes were isolated and stimulated with isoproterenol (ISO) or phenylephrine (PHE) to induce myocardial hypertrophy.ResultsThrough single-cell RNA-seq analysis, immunofluorescent staining, HE staining, Western blotting, and real time-PCR detections, we found that YTHDF2 mRNA and protein level, but not YTHDF1 or YTHDF3, was significantly increased during HF development. YTHDF2 overexpression could efficiently alleviate cardiac hypertrophy. Furthermore, through immunoprecipitation accompanied with mass spectrometry analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that ISO stimulation did not evidently affect YTHDF2-interacting proteins. However, ISO or PHE stimulation significantly increased YTHDF2 protein interacting with Myh7 (beta-myosin heavy chain) mRNA, an important cardiac hypertrophy marker, in an m6A-dependent manner. Knockdown of Myh7 or deletion of the YTH domain of YTHDF2 reversed the protective effects of YTHDF2 on cardiac hypertrophy. Finally, we found that ISO or PHE stimulation promoted YTHDF2 protein expression through enhancing Ythdf2 mRNA stability in an m6A-dependent manner in cardiomyocytes.ConclusionsOverall, our results indicate that the m6A Reader YTHDF2 suppresses cardiac hypertrophy via Myh7 mRNA decoy in an m6A-dependent manner. This study highlights the functional importance of YTHDF2-dependent cardiac m6A mRNA regulation during cardiac hypertrophy, and provides a novel mechanistic insight into the therapeutic mechanisms of YTHDF2.

Dataset Information

YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m⁶A/mRNA pathway.

Publications

YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m<sup>6</sup>A/mRNA pathway.

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Dataset Information

YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m6A/mRNA pathway.

Publications

YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m<sup>6</sup>A/mRNA pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m⁶A/mRNA pathway.