title: The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells.
abstract: The Piwi-piRNA pathway is active in animal germ cells where its functions are required for germ cell maintenance and gamete differentiation. Piwi proteins and piRNAs have been detected outside germline tissue in multiple phyla, but activity of the pathway in mammalian somatic cells has been little explored. In particular, Piwi expression has been observed in cancer cells, but nothing is known about the piRNA partners or the function of the system in these cells. We have surveyed the expression of the three human Piwi genes, Hiwi, Hili and Hiwi2, in multiple normal tissues and cancer cell lines. We find that Hiwi2 is ubiquitously expressed; in cancer cells the protein is largely restricted to the cytoplasm and is associated with translating ribosomes. Immunoprecipitation of Hiwi2 from MDAMB231 cancer cells enriches for piRNAs that are predominantly derived from processed tRNAs and expressed genes, species which can also be found in adult human testis. Our studies indicate that a Piwi-piRNA pathway is present in human somatic cells, with an uncharacterised function linked to translation. Taking this evidence together with evidence from primitive organisms, we propose that this somatic function of the pathway predates the germline functions of the pathway in modern animals.
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia Faculty of Engineering and Information Technology, Centre of Health Technologies, University of Technology Sydney, 235 Jones Street, Ultimo, NSW, 2007, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Keam
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Young
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: McCorkindale
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia.
authors.forename: Thurston H Y
authors.initials: TH
authors.lastname: Dang
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Clancy
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia.
authors.forename: David T
authors.initials: DT
authors.lastname: Humphreys
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Preiss
authors.affiliation: Faculty of Engineering and Information Technology, Centre of Health Technologies, University of Technology Sydney, 235 Jones Street, Ultimo, NSW, 2007, Australia.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Hutvagner
authors.affiliation: Center for Genetics, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
authors.forename: David I K
authors.initials: DI
authors.lastname: Martin
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia Faculty of Medicine, University of New South Wales, Kensington, 2052, Australia c.suter@victorchang.edu.au.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cropley
authors.affiliation: Molecular, Structural and Computational Biology Division, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW, 2010, Australia Faculty of Medicine, University of New South Wales, Kensington, 2052, Australia c.suter@victorchang.edu.au.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Suter
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D015894:Genome, Human; D006801:Humans; D011506:Proteins / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000378:metabolism*; D058727:RNA, Small Untranslated / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism*; D016601:RNA-Binding Proteins
chemical_list: C556795:PIWIL4 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D058727:RNA, Small Untranslated; D016601:RNA-Binding Proteins; D012343:RNA, Transfer