Non-coding RNAs enter mitosis: functions, conservation and implications

Germline granules were first described in rat spermatids more than 100 years ago and were subsequently named "chromatoid bodies" in mammalian cells [1,2]. They were later found to be widely-conserved in germline cells of many animals, where they are referred to as "nuage" and "P granules" in Drosophila melanogaster and Caenorhabditis elegans, respectively [3,4]. Under the electron microscope, germline granules appear as electron-dense fibrous structures, are not bound by any membrane and localize to the cytoplasmic peri-nuclear region [3]. Since their discovery, germline granules have remained mysterious due to the fact that their precise function has not been identified.Recent studies in Drosophila have linked these germline granules (hereafter referred to as nuage) to a novel class of small non-coding RNAs known as Piwi-interacting RNAs (piRNAs). piRNAs are a class of gonadal-specific RNAs that are ~23-29 nucleotides in length and produced in a Dicer-independent manner [5-9]. They are mainly derived from transposons or repetitive sequences that are clustered in the peri-centromeric and sub-telomeric regions of the chromosome [10,11]. Interestingly, many proteins that are required for the biogenesis of piRNAs are found to localize to the nuage. For example, in Drosophila, the PIWI subfamily proteins, Aubergine and Argonaute3, which bind piRNAs, are components of the nuage [11-14]. In mouse, the PIWI family proteins, MILI and MIWI, also localize to the chromatoid body [5]. In the Drosophila nuage, Aubergine and Argonaute3 are believed to function in a secondary piRNA amplification pathway known as the "ping-pong" cycle in germline cells [11,15]. Other germline piRNA pathway proteins, such as Vasa (Mouse Vasa Homolog), Spindle-E (mouse TDRD-9), Krimper, Maelstrom (mouse Maelstrom), Cutoff (yeast Rai1) and Tejas (mouse TDRD-5 and TDRD-7), also localize to nuage although their exactly molecular function in piRNA processing remains unknown [16-20]. Of note, some piRNA p