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.
Highlights
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction Male fertility depends on spermatogenesis, which is a complicated and highly controlled process that consists of mitosis of spermatogonia, meiosis of spermatocyte and spermiogenesis[1]
Growing evidence indicate that m6A is involved in various biological processes, such as cell differentiation, stem cell fate, cardiac remodeling, and cancer progression4. m6A is a dynamic and reversible modification, which is catalyzed by the methyltransferase complex composed by WTAP, METTL3, METTL14, and other m6A “writers”[5]
The PGL-sgRNA plasmids and the pST374-Cas[9] plasmids were co-transfected to the mouse GC-1 spermatogonial cell line
Summary
Male fertility depends on spermatogenesis, which is a complicated and highly controlled process that consists of mitosis of spermatogonia, meiosis of spermatocyte and spermiogenesis[1]. Spermatogonia are the foundation of sperm production[2]. M6A is a dynamic and reversible modification, which is catalyzed by the methyltransferase complex composed by WTAP, METTL3, METTL14, and other m6A “writers”[5]. Growing evidence indicate that m6A is involved in various biological processes, such as cell differentiation, stem cell fate, cardiac remodeling, and cancer progression. This modification can be removed by the m6A “eraser” proteins FTO and ALKBH56,7. M6A domain-containing proteins (YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2), eIF3 and IGF2BP28
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