Researchers have identified the spatial arrangement of approximately 700 long non-coding RNAs, commonly referred to as lncRNAs, within the testes. Their findings reveal a significantly greater abundance of lncRNAs in the testes than previously thought, suggesting that these molecules may have a more critical role in male reproduction than was once acknowledged.
Researchers at the University of Toronto have identified the spatial arrangement of approximately 700 long non-coding RNAs, commonly referred to as lncRNAs, within the testes. Their findings reveal a significantly greater abundance of lncRNAs in the testes than previously thought, suggesting that these molecules may have a more critical role in male reproduction than was once acknowledged.
The research team carried out a comprehensive analysis of lncRNA localization within the testes of the fruit fly, a widely used model organism in biomedical studies. They discovered that both the count and the expression levels of lncRNA genes were much higher than anticipated, challenging prior assumptions about their insignificance, which stemmed from the idea that lncRNAs do not produce proteins.
“Long non-coding RNAs generate debate because their functions remain largely elusive, if they have any,” stated Matthew Jachimowicz, a co-author of the study and a PhD student in molecular genetics at the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research. “The prevailing uncertainty surrounding lncRNAs is partially rooted in the assumption that they are expressed at low levels across different genomes. Our findings contradict this view and present numerous potential roles for lncRNAs in the evolution and development of sperm.”
The study has been published in the journal Nature Communications.
Throughout the animal kingdom, the development of sperm involves the highest gene expression levels, where lncRNA genes are expressed even more abundantly than coding genes, and for extended periods. The Y chromosome, which is exclusively expressed during sperm maturation, poses particular challenges for researchers due to its unique genetic properties, including transposable elements, satellite repeats, and pseudogenes.
Transposable elements are DNA sequences capable of relocating within the genome. Satellite repeats consist of larger segments of repetitive DNA sequences, while pseudogenes have structures akin to genes but do not code for proteins.
The existence of these repetitive non-coding elements in the Y chromosome leads to its silencing during all developmental stages except for sperm production. However, they could endanger sperm by integrating non-coding elements into crucial genes, resulting in mutations, sperm dysfunction, or birth defects.
The research team identified lncRNA genes that could mitigate the potentially harmful activities of transposable elements, maintaining them at a level conducive to the advancement of new genes rather than triggering mutations in existing genes.
“Research has shown that mature sperm contain RNA from both coding and non-coding genes,” remarked Jachimowicz. “The presence of non-coding RNA in the sperm nucleus can influence metabolic processes and behaviors for several generations.”
The research group also uncovered a novel type of lncRNA-based particle within seminal fluid, which may play a role in reproduction and affect offspring. They propose that these new lncRNA-based particles could originate from both sperm and non-sperm cells, potentially transmitting intricate intercellular signals.
“Many of the lncRNAs we identified were overlooked in prior research because they lack polyadenylation,” explained Catherine Shao, the study’s lead author and lab technician at the Donnelly Centre. “This process involves adding a tail of adenine nucleotides to the RNA molecule, which stabilizes it and prevents degradation. It turns out that most lncRNAs are not polyadenylated, which is why conventional detection methods missed so many of them.”
“Our discovery of elevated lncRNA expression in the testes is crucial in debunking the notion that lncRNAs are predominantly non-functional, a belief substantially based on observations of low expression levels,” stated Henry Krause, the principal investigator of the study and a professor of molecular genetics at the Donnelly Centre and the Temerty Faculty of Medicine. “In particular, the newly found lncRNA-based particles have the potential to contribute to the creation of novel RNA-based therapies.”
