Positioning of sperm tail longitudinal columns depends on NSUN7, an RNA-binding protein destabilizing elongated spermatid transcripts.

Abstract

Spermatozoid's flagella assemble in transcriptionally silent spermatids and thus depend on posttranscriptional regulation of gene expression. Mutations in Nsun7 gene are known to cause male infertility in human and mice. We identified m⁵C-specific NSUN7 RNA methyltransferase as a protein present in elongated spermatids and interacting with RNAs specific for this type of spermatozoid's precursor cells. Inactivation of the Nsun7 gene in mice leads to upregulation of its RNA interactors, thus indicating that NSUN7 downregulates a set of RNAs in the elongated spermatids. A physiologic consequence of Nsun7 gene knockout is male infertility, which is mechanistically explained by the observed mispositioning of longitudinal columns relative to the axonemal microtubular doublets leading to a motility defect.