The paternal genome genomes an enormous trade of histone with protamine for compaction into sperm during spermiogenesis. Upon fertilization, this procedure is potently reversed, which is essential for parental genome reprogramming and subsequent activation; however, it remains poorly understood how this vital procedure is initiated and regulated.
Scientists at the University of California San Diego School of Medicine have found that the enzyme SPRK1 leads the first step in untangling a sperm’s genome, kicking out particular packing proteins, which opens up the paternal DNA and allows for significant reorganization—all surprisingly fast.
Xiang-Dong Fu, Ph.D., Distinguished Professor in the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine, said, “In this study, we were simply interested in answering a fundamental question about the beginning of life. But in the process, we’ve uncovered a step that might malfunction for some people and contribute to a couple’s difficulty conceiving. Now that we know SPRK1 plays a role here, its potential part in infertility can be further explored.”
Sperm can be up to multiple times smaller than a normal cell in the body. And while sperm carry just half as much genetic material as a regular cell, it should be folded and packaged in an extraordinary manner to fit. One way nature does this is by replacing histones—proteins around which DNA is wound, similar to beads on a neckband—with another sort of protein called protamines.
SPRK1 can splice RNA. This is an essential step that enables the translation of genes to proteins.
Previously, scientists indicated that SPRK1 is over-actuated in colon cancer, and they developed inhibitors to dampen the enzyme.
But back in 1999, shortly after Fu published a paper that first described the enzyme’s role in RNA splicing, a research group in Greece noted similarities in the sequence of amino acid building blocks that make up SPRK1 substrates (the proteins upon which the enzyme acts) and protamine.
Fu thought about it for years but didn’t have the expertise and tools to study sperm development. In 2015, he met with Lan-Tao Gou, Ph.D., an expert in spermatogenesis.
Fu said, “I said to Lan-Tao, let’s do something nobody else is doing. I have a theory, and you have the expertise. So we borrowed the equipment we needed and leveraged the core facilities we have here at UC San Diego.”
“And, surprisingly, everything we tried supported our hypothesis—SRPK1 leads a double life, swapping protamines for histones once sperm meets egg.”
“SPRK1 most likely started out playing this role in early embryogenesis, then later evolved the ability to splice RNA. In this way, SPRK1 gets to stick around even when it’s no longer needed for embryogenesis.”
Scientists further aim to determine the signals that instruct sperm to synchronize with the maternal genome.
Fu said, “We have a ton of new ideas now. And the better we understand every step in the process of spermatogenesis, fertilization, and embryogenesis, the more likely we are to be able to intervene when systems malfunction for couples struggling with reproductive issues.”
The study was published in the journal Cell.