Mighty Piwis

April 7, 2008

Last year Kathryn O’Donnell and Jef Boeke published a review in Cell on Piwis and their role in maintaining transposon silencing in the germline genome. Together with an additional short review by Seto et. al. on Piwi proteins, a compelling picture of Piwis is just beginning to emerge … In brief,

“.. the recent characterization of the molecular function of Piwis (P element-induced wimpy testes) proteins, a novel form of control for mobile elements has emerged involving small RNAs in germ line.”

A small number of specific loci in Drosophilia produce large numbers of piRNAs (Piwi interacting RNAs) which direct Piwi proteins to cleave transposon targets. There appears to be a self-reinforcing amplification cycle induced by the cleave event, as cleaved transposons result in sense piRNAs which direct cleavage of the original genomic piRNA cluster. Unanswered questions exist concerning how the cycle is initiated and what prevents constitutive autoamplification (perhaps cellular localization) still exist. Nevertheless, the proposed piRNA mechanism opens yet another chapter in the saga that is non-coding RNAs as regulators.

While the conservation of the mechanism is yet to be established, Piwi orthologs are being studied in at least flies, mice, and zebrafish. Piwi proteins exist in a number of organisms (including ciliates and slime molds) implying that their function may also be conserved. Furthermore, there are some lines of evidence suggesting that the mammalian Piwis may have acquired additional germline-specific functions besides regulating repetitive elements. Piwi proteins may serve an epigenetic role in nuclear surveillance, but currently this is unclear as there is evidence both for and against this hypothesis. So, we are still at the very early stages of understanding piRNAs and their function. Therefore this is an area of research with many open questions.

But the use of piRNAs as a defense mechanism against runaway selfish elements (transposons) is an attractive idea. It also implies that some regions of the genome, containing apparent graveyards of transposable elements, may in fact be storage banks necessary for defensive surveillance. Repeat elements comprise the majority of animal genomes, therefore cells must effectively deal with this complex and poorly understood bulk sequence. A deeper understanding of Piwi proteins and piRNAs has implications on understanding fertility, stem cell development, evolution of genomes, and regulation.

ODONNELL, K., BOEKE, J. (2007). Mighty Piwis Defend the Germline against Genome Intruders. Cell, 129(1), 37-44. DOI: 10.1016/j.cell.2007.03.028

SETO, A., KINGSTON, R., LAU, N. (2007). The Coming of Age for Piwi Proteins. Molecular Cell, 26(5), 603-609. DOI: 10.1016/j.molcel.2007.05.021

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