Enigmatic Pachytene PIWI-Interacting RNAs

Abstract

PIWI-interacting RNAs (piRNAs), a class of small RNAs, are renowned for their roles in sequencing-dependent targeting and suppressing transposable elements (TEs). Nevertheless, a majority of mammalian piRNAs, expressing at pachytene stage of meiosis, known as pachytene piRNAs, are devoid of discernible targets, casting a veil of enigma over their functional significance. Overturning the notion that this unusual class of piRNAs functions beyond TE silencing, we recently demonstrated that pachytene piRNAs play an essential and conserved role in silencing young and actively transposing TEs across amniotes. However, only 1% of pachytene piRNAs target active TEs. The biological significance of the abundant non-TE piRNAs, coproduced from the same precursors as TE piRNAs, remains unclear. Here, we provide a comprehensive summary of the potential roles of non-TE piRNAs, and thus propose that these non-TE piRNAs either bolster the action of TE piRNAs or provide the host genome a preexisting mechanism to suppress the potential invasion of novel TEs in the future.

Keywords: evolvability; piRNA; transposable element.

Fig. 1.

A comparison of miRNA and piRNA pathways.

Fig. 2.

Three accelerators of pathytene piRNA evolution. This schematic representation illustrates the dynamic forces propelling the swift evolution of pathytene piRNAs. The model elucidates three pivotal drivers. (Middle) Local mutation rate and SVs: piRNA genes undergo a substantial local mutation rate, leading to the emergence of novel piRNAs through SVs. These genetic changes contribute to the diversity and adaptability of the piRNA repertoire. (Left) Positive selection in germ cells: Within germ cells, positive selection operates to selectively suppress active TEs through piRNAs. This process is crucial for maintaining genome integrity and ensuring the fidelity of genetic information transmission to the next generation. (Right) Negative selection in somatic cells: Conversely, detrimental effects on nearby protein-coding gene operate in somatic cells, driving the elimination of detrimental SVs from the piRNA pool. This negative selection prevents potentially harmful mutations in non-germline tissues from inheriting by the next generation. Together, these forces orchestrate the intricate evolution of pathytene piRNAs, optimizing their functionality in diverse biological contexts.

Fig. 3.

Proposed hypotheses explaining the existence of non-TE piRNAs. a) By-products coinciding with TE piRNAs without a distinct function. b) Residual functions from the past that are being phased out. c) Mutualistic roles that enhance the production or efficacy of TE piRNAs. d) Potential future roles in TE defense, considering the unpredictable nature of TE invasions and the vast diversity among TE families.