An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning

Area of Science:

• Reproductive Biology
• Molecular Biology
• Genetics

Background:

• RBMXL2 is an ancient nuclear RNA binding protein found in male germ cells of placental mammals.
• Its function has remained largely unknown despite its conserved presence.

Purpose of the Study:

• To investigate the function of RBMXL2 in male germ cell development.
• To determine the role of RBMXL2 in regulating gene expression and splicing during meiosis.

Main Methods:

• Generation and analysis of RBMXL2 deletion mice.
• Transcriptome analysis (RNA sequencing) of germ cells from wild-type and RBMXL2-deficient mice.
• Splicing pattern analysis to identify aberrant splicing events.

Main Results:

• Deletion of the RBMXL2 gene completely blocks spermatogenesis.
• RBMXL2 is essential for controlling RNA splicing patterns during male meiosis.
• RBMXL2 actively represses the use of aberrant splice sites, including cryptic and premature terminal exons.

Conclusions:

• The RBMXL2 retrogene plays a critical, conserved role in mammalian germ cell biology.
• RBMXL2 functions as a splicing regulator, preventing gene expression disruption during meiosis.
• This mechanism is vital for meiosis, potentially by buffering splicing activators and preventing aberrant splice site selection.