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

Cell Death Dis. 2020 Jan 20;11(1):37. doi: 10.1038/s41419-020-2235-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Animals
  • Apoptosis
  • CRISPR-Associated Protein 9 / metabolism
  • CRISPR-Cas Systems / genetics
  • Cell Adhesion / genetics
  • Cell Cycle
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Extracellular Matrix / metabolism
  • Gene Deletion
  • Gene Expression Regulation
  • Male
  • Matrix Metalloproteinases / metabolism*
  • Mice, Knockout
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spermatogonia / cytology*
  • Spermatogonia / metabolism

Substances

  • RNA, Messenger
  • RNA-Binding Proteins
  • YTHDF2 protein, mouse
  • N-methyladenosine
  • CRISPR-Associated Protein 9
  • Matrix Metalloproteinases
  • Adenosine