Homeland security in the C. elegans germ line: insights into the biogenesis and function of piRNAs

Abstract

While most eukaryotic genomes contain transposable elements that can provide select evolutionary advantages to a given organism, failure to tightly control the mobility of such transposable elements can result in compromised genomic integrity of both parental and subsequent generations. Together with the Piwi subfamily of Argonaute proteins, small, non-coding Piwi-interacting RNAs (piRNAs) primarily function in the germ line to defend the genome against the potentially deleterious effects that can be caused by transposition. Here, we describe recent discoveries concerning the biogenesis and function of piRNAs in the nematode Caenorhabditis elegans, illuminating how the faithful production of these mature species can impart a robust defense mechanism for the germ line to counteract problems caused by foreign genetic elements across successive generations by contributing to the epigenetic memory of non-self vs. self.

Keywords: 22G-RNA; Argonaute proteins; C. elegans; Piwi/PRG-1; biogenesis; epigenetics; germ line; piRNA/21U-RNA; transgenerational silencing.

Figure 1. Biogenesis and function of C. elegans 21U-RNAs. (Top) In germline nuclei (green), 21U-RNA genes located primarily on two clusters on Chr. IV are individually transcribed by Forkhead (FKH) transcription factors and RNA polymerase II (RNAP II). 21U-RNA precursors are further processed to their functional form in P granules (purple), where they associate with the Piwi Argonaute protein PRG-1. Targeting by imperfect base pairing of mature PRG-1/21U-RNA complexes to non-self transcripts triggers the formation of 22G-RNAs, which subsequently leads to foreign transcript silencing. WAGO-associated 22G-RNAs are shuttled back into the nucleus, where they function in transcriptional gene silencing via mechanisms likely involving the formation of repressive chromatin, including the placement of the heterochromatic mark H3K9me3. CSR-1/22G-RNAs counteract PRG-1/21U-RNA activity by licensing transcripts as self-elements, and thereby preventing their degradation. (Middle) Schematic of one gonad arm of a C. elegans adult hermaphrodite. (Bottom) During oogenesis, P granules begin to dissociate from nuclear pores and CSR-1 also localizes to the nucleus. Licensing of self-transcripts putatively occurs by shuttling of CSR-1/22G-RNAs into the nucleus, where they function in the maintenance of germline gene expression by promoting the formation of active chromatin. Yellow circles with question marks denote unknown factors in biogenesis and functional pathways, and dashed arrows indicate activities that are assumed to occur.