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, 42 (12), 828-835

PIWI Proteins and piRNAs in the Nervous System


PIWI Proteins and piRNAs in the Nervous System

Kyung Won Kim. Mol Cells.


PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.

Keywords: neurological disorders; non-coding RNA; posttranscriptional gene silencing; small RNA; transposable elements.

Conflict of interest statement


The author has no potential conflicts of interest to disclose.


Fig. 1
Fig. 1. The molecular mechanisms of the PIWI-piRNA pathway
The PIWI protein and piRNA form a complex, called piRNA-induced silencing complex (piRISC). piRISC regulates targeted RNAs, including transposable elements and endogenous target mRNAs, via transcriptional gene regulation (TGS) or post-transcriptional gene regulation (PTGS). TGS is often mediated through the recruitment of a chromatin methylation complex to the nucleus inducing a heterochromatin state, which serves as a repressive mark. TGS can also be mediated by recruiting DNA methyltransferases. PTGS is often mediated by the endonuclease activity of the PIWI protein resulting in cleavage of the target mRNA in the cytoplasm.
Fig. 2
Fig. 2. PIWI proteins
(A) Domains of the PIWI protein. (B) PIWI homologs expressed in various model organisms.
Fig. 3
Fig. 3
The roles of the piRNA pathway in neurons of various organisms.

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