Xiol, J., Pietro Spinelli, Laussmann, M.A., Homolka, D., Yang, Z., Cora, E., Couté, Y., Conn, S., Kadlec, J., Sachidanandam, R., Kaksonen, M., Cusack, S., Ephrussi, A., Pillai, R.S., 2014. RNA Clamping by Vasa Assembles a piRNA Amplifier Complex on Transposon Transcripts. Cell 1–20. doi:10.1016/j.cell.2014.05.018
A truly sick pape, like any great work of art, weaves together the threads of many diverse historical influences into an intricate - and preferably blacklight sensitive - tapestry. Thus, a true artist reveals a web of connections between his or her historical predecessors, connections that may seem obvious in hindsight, but which would in fact never have existed without the artist’s work. For example, consider two of the major literary works that have influenced us here at Sick Papes™: How To Bag The Biggest Buck of Your Life by Larry Benoit, and Untruths About Animals by Orville Lindquist. Without our important artistic output, the now-obvious spiritual kinship between these two masterpieces would have been lost on a generation of biologists. This is undoubtedly what Borges meant when he wrote that “every writer creates his own precursors.”
Today’s Pape weaves together two particularly deep and powerful historical threads. The first is a 16th century Swedish King; the second is the epic world-historical tale of the silk industry. When these two stories come together on the loom of cell culture and in vivo validation, you’ve got yourself a fucking insane tapestry.
King Gustav Vasa (1496-1560) was the patriarch the Vasa noble family of Sweden, which ruled until 1654, when the family died off with no heirs. This lack of heirs is the reason why Vasa is also the namesake of the vasa gene: when the first group of sterility genes were identified in Drosophila (i.e. those mutations that cause sterility), these genes were all named after extinct European royal families that had left no heir: Vasa, Tudor, Valois, Staufen. Vasa is a molecular marker for germ cells of nearly all animals, which makes it a very fascinating and widely studied gene. Infuriatingly, however, we still don’t have a clear understanding of exactly why this gene is necessary for producing heirs.
Keep that in mind as you allow your mind to drift to China in 3,000-5,000 B.C., when people first domesticated the silkmoth. For the following 7,000 years, we have been going nucking futs for silk, and have continued to pour unimaginable resources into understanding the biology of this wildass insect. Whereas Drosophila has flourished as a model organism because of its relatively simple genetics and rapid reproduction, the silkworm Bombyx mori has none of these advantages (i.e. it’s got 28 pairs of chromosomes and is wicked friggin’ labor intensive to keep). But our insatiable need to be clothed in silk at all times has kept this bugger well-studied for thousands of years.
One of the completely unpredictable outcomes of all the silkworm research has been the discovery of an immortalized cell line where a very specific biological pathway is active: the Piwi pathway. (The Piwi gene, like Vasa, is necessary for ferility, but it’s namesake is not European royalty but rather an acronym for “P-element induced wimpy testis”). The Piwi pathway, which we’ve spoken about before, is a recently discovered pathway that utilizes small RNA molecules (“piRNAs”) to protect the genome against transposons and other pieces of destructive jumping DNA. The silkworm-derived cell line is apparently the only cell line currently known where the Piwi pathway is active, and therefore provides one of the most biochemically tractable opportunities to pick apart this freaky pathway.
These data monsters use the silkworm cell line to uncover a direct physical connection between Vasa and the Piwi pathway: it turns out that Vasa protein molecules are the physical location where the small piRNA precursors are exchanged between members of the Piwi pathway, allowing them to serve as templates to destroy transposons. Thus, it turns out after all these years that Vasa is essentially part of the Piwi pathway, and that one of the major functions of this mysterious genes is to protect the genomic damage caused by transposons, which is especially critical in germ cells and other types of stem cells, where genomic injury can have particularly gnarly consequences. And thus, the true purpose of the past 7,000 years of silk cultivation, European monarchy, and Cell Press has finally been revealed, and for this we celebrate.
