Abstract
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.
Highlights
Piwi protein is expressed in animal germ cells, regulating a series of reproductive-related events, such as reproductive stem cell self-renewal and maintenance and germ cell development and differentiation
The quantified sequence data was consistent, with respect to the expression levels of the Piwi-interacting RNA (piRNA), with the quantitative real-time polymerase chain reaction (qPCR) results (Figure 3D). These results show that piRNAs expression decreased significantly with age and suggest that the role the mitochondrial COX1 variation has in regulating reproduction and aging may influence piRNAs levels related to these processes
Previous studies have suggested that piRNAs provide heritable, sequence-specific triggers for RNA interference in C. elegans (Bagijn et al, 2012)
Summary
Piwi protein is expressed in animal germ cells, regulating a series of reproductive-related events, such as reproductive stem cell self-renewal and maintenance and germ cell development and differentiation. Piwi protein has been found to bind to a recently discovered type of non-coding RNA, named piRNA This interaction has been found to play an important role in germline DNA integrity (Klattenhoff and Theurkauf, 2008), embryonic development (Du et al, 2016), immune defense [2] and cancer prediction (Zhang et al, 2016), etc. Most piRNA sequences are not highly conserved, but their location in the genome is highly conserved (Girard et al, 2006) As reproduction plays such an important role in the process of evolution because it is the basis for the continuation of populations, the roles of Piwi in gametogenesis and the conserved locations of piRNA coding regions suggest the Piwi-piRNA pathway has an evolutionarily conserved role in the regulation of reproduction in animals (Bagijn et al, 2012)
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