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New Insights Into Male Infertility

Researchers discover a potential role for the RNA-binding protein, RBMXL2, in spermatogenesis.

Image source: https://www.shutterstock.com/image-photo/dna-molecules-on-beautiful-backdrop-134698571

Spermatogenesis, the creation mature spermatozoa, is a complex process. During spermatogenesis, germ cells undergo meiosis - a kind of cell division that results in the creation of genetically unique gametes. This process involves many supporting proteins.


Steps of Meiosis. Image source: https://commons.wikimedia.org/wiki/File:Mitosis_schematic_diagram-en.svg

One example of these supporting proteins are splicing proteins, which bind to RNA and modify it into sequences required to make desired proteins.


RBMXL2 is a protein that is only produced during and immediately after meiosis. While the exact role of this protein is unclear, its tendency to bind to RNA and splicing proteins was what sparked the interest of researchers at Newcastle University to investigate whether RBMXL2's association with splicing proteins has a significant effect on spermatogenesis.


While the researchers found that RBMXL2 knockout mice developed similarly to wild type mice, their testes size was significantly smaller, and they did not express any post-meiotic germ cells.


Further investigation led to the discovery in RBMXL2 knockout mice, cells underwent meioisis up until the diplotene phase of prophase, after which apoptosis occurred. This suggests that RBMXL2 plays an important role in preventing mis-splicing of genes important for meiosis, such as meioic (meiosis specific gene with coiled coil domain). Meioic exon five (normally conserved across species) is controlled by RMBXL2, which binds to it and prevents splicing at cryptic splicing sites. The researchers found that in the absence of RBMXL2, missplicing occurs at the prophase step of meiosis (when RMBXL2 is normally expressed). The researchers mention that cells in prophase may be particularly sensitive to missplicing as they have high levels of transcription, unique expression of splice site regulators, and relaxed chromatin environments. Thus, functional RBMXL2 is essential at this stage of meiosis.

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