In this review, we follow the life of piRNAs from their biogenesis to their canonical role in silencing transposons and to their latest roles in neurological function and dysfunction. Moreover, the number of piRNAs discovered is increasing rapidly.

In recent years, piRNAs have been shown not only to protect germline genome against transposon mobilization to maintain the genome stability, but also to participate in neuronal growth and development, metabolic homeostasis, self-renewal of stem cells, cancer, and processes of neurodegenerative diseases. The role of piRNAs in silencing unwanted germline transcripts and maintaining genome integrity has been studied in detail, but their role in somatic cells is less clear. Finally, most miRNAs degrade mRNA directly, while piRNAs can cleave mRNA directly or induce transcriptional silencing by recruiting histone 3 lysine 9 tri-methylation (H3K9me3) and histone methyltransferase to induce histone modification or DNA methylation. In addition, piRNAs use the ping-pong cycle to amplify the piRNA signal in Drosophila and mice, or recruit an RNA-dependent RNA polymerase to synthesize massive secondary small interfering RNAs (22G-RNAs) during the biogenesis process, whereas miRNAs are transcribed from the genome without amplification. miRNA is a small duplex RNA with a 5′ monophosphate and a 2′,3′ hydroxyl, 2-nt overhanging 3′ end, while piRNAs typically have a uridine at the 5' end and 2′- O-methylation at the 3′ end. Third, miRNA and piRNA have different chemical structures. miRNA is 21–25-nucleotide (nt) long, while the piRNA is 24–32 nt in most species with exception in C. In contrast, miRNA originates from a double-stranded precursor and the primary miRNA transcript is processed by Drosha to generate a pre-miRNA, which is then further modified by Dicer to become a mature miRNA. First, piRNA is processed from a single-stranded precursor transcribed from a piRNA cluster and the biogenesis does not require Drosha or Dicer proteins.

There are several differences between microRNA (miRNA) and piRNA. PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs widely existing in nematodes, insects, zebrafish, Drosophila, Aplysia and mammals that regulate transposon and gene expression. Understanding the roles of piRNAs in neurological diseases may facilitate their applications in diagnostic and therapeutic practice. We speculate on the mechanisms of piRNA action in the development and progression of neurodegenerative diseases. Lastly, the most recent findings on piRNA participation in neurological diseases are highlighted. elegans, Drosophila, and mice, and further elaborate upon how piRNAs mitigate the harmful effects of transposons. In this review, we summarize piRNA biogenesis in C. In the recent decade, emerging roles of piRNAs have been revealed, including the roles in sterility, tumorigenesis, metabolic homeostasis, neurodevelopment, and neurodegenerative diseases. piRNAs were originally discovered in germline cells and protect against transposable element expression to promote and maintain genome stability. PIWI-interacting RNAs (piRNAs) are small non-coding transcripts that are highly conserved across species and regulate gene expression through pre- and post-transcriptional processes.

Decipher messenger export