piRNAs Regulated by Mitochondria Variation Linked With Reproduction and Aging in Caenorhabditis elegans


In Caenorhabditis elegans, the binding of Piwi protein to a non-coding RNA form, called piRNA, has been found to be important to both reproductive and aging processes. As the biosynthesis of piRNA is modulated by mitochondrial function, it is likely that the interaction between mitochondrial function and piRNA expression plays an unknown, yet important, role in reproductive and aging processes because both processes are known to be affected by declines in mitochondrial quality and activity. While the relationship between reproduction and longevity is not characterized in full, the optimality theory of aging and the disposable soma theory suggest that a trade-off between energy and resources is needed for reproductive and aging maintenance. In this study, the influence of mitochondrial variations, via a respiratory chain complex IV (COX1) polymorphism, on piRNA expression was examined in relation to the reproductive and aging outcomes of C. elegans. The COX1 polymorphism in mitochondria was found to affect the number of piRNAs expressed, the development of germ cells, and the length of the lifespan of the nematodes. Interestingly, more than two-thirds of the piRNA expression changes associated with the mitochondrial variation were found to also be affected by age. A gene ontology analysis of the altered piRNA species found that the piRNAs affected by mitochondrial variation and age were linked to genes known to have roles in reproductive and developmental function. Moreover, a piRNA-lncRNA-mRNA regulatory network based on the differential expression patterns of piRNA related to the mitochondrial variation was constructed to further identify potential gene targets with functional interactions. Similarly, this network identified genes involved in reproduction, development, and aging processes. These findings provide new insight into understanding how mitochondrial variations may regulate piRNA expression and may influence the underlying molecular mechanisms that affect reproduction and aging.


The Piwi–piRNA pathway has been evolutionarily conserved in many germlines (Bagijn et al., 2012). In C. elegans, piRNAs are about 20 nucleotides in length and have a 5’ uracil nucleotide end (Ruby et al., 2006). Previous studies have suggested that piRNAs provide heritable, sequence-specific triggers for RNA interference in C. elegans (Bagijn et al., 2012). Interestingly, most of these previous studies on piRNAs focused on reproduction, and a few studies were related to aging (Kim and Lee, 2019). Moreover, studies have confirmed that mitochondria function is required for Piwi-interacting RNA (piRNA)-mediated silencing of transposable elements in fly and mouse germlines, suggesting that mitochondria play an important role in piRNA pathway (Aravin and Chan, 2011). Thus, piRNAs may play a link role between mitochondria and reproduction and aging. In this study, C. elegans was used as a model organism to explore the relationship among mitochondria, piRNA, reproduction, and aging.

Since the piRNA pathway has been found to be influenced by mitochondria and is involved in the regulation of reproductive function and aging, it was hypothesized that mitochondria influence reproduction and aging through piRNAs. Mitochondrial genes account for only a very small part of an organism’s genome, but the mitochondria provide the necessary energy for cellular function and play an important role in signal transduction, cell growth, and apoptosis. Our previous studies had shown that the degree of mismatch between the mitochondria and nuclear genome may be an important factor that influences reproduction and lifespan differences among C. elegans populations (Zhu et al., 20152019). These earlier studies included the construction of a nuclear transfer C. elegans germline containing a COX1 mitochondrial gene variation and the same genomic background as wild-type nematodes (Bristol Strain) and found the germline to have reduced mitochondrial function relative to N2 C. elegans and to have reduced function related to reproduction and

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