N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis.

ABSTRACT:

Background

The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive.

Results

We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes.

SUBMITTER: Ma Q 

PROVIDER: S-EPMC11264951 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature