The PIWI Proteins SMEDWI-2 and SMEDWI-3 Are Required for Stem Cell Function and PiRNA Expression in Planarians

Overview

Journal RNA

Specialty Molecular Biology

Date 2008 May 6

PMID 18456843

Citations 122

Authors

Dasaradhi Palakodeti

Magda Smielewska

Yi-Chien Lu

Gene W Yeo

Brenton R Graveley

Affiliations

Soon will be listed here.

Abstract

PIWI proteins are expressed in germ cells in a wide variety of metazoans, where they participate in the synthesis and function of a novel class of small RNAs called PIWI associated RNAs (piRNAs). One function of piRNAs is to preserve the integrity of the germline genome by silencing transposons, though they also participate in epigenetic and post-transcriptional gene regulation. In the planarian Schmidtea mediterranea, the PIWI proteins SMEDWI-1 and SMEDWI-2 are expressed in neoblasts and SMEDWI-2 is required for regeneration and homeostasis. Here, we identify a diverse population of approximately 32-nucleotide small RNAs that strongly resemble vertebrate and insect piRNAs and map to hundreds of thousands of loci in the S. mediterranea genome. The expression of these RNAs occurs predominantly in neoblasts and is not restricted to the germline. RNAi knockdown of either SMEDWI-2 or a newly identified PIWI protein, SMEDWI-3, impairs regeneration and homeostasis and decreases the levels of both piRNAs and neoblasts. Therefore, SMEDWI-2 and SMEDWI-3 are required for piRNA expression, regeneration, and neoblast function in S. mediterranea.

Citing Articles

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Stem cells (neoblasts) and positional information jointly dominate regeneration in planarians.

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References

Aravin A, Sachidanandam R, Girard A, Fejes-Toth K, Hannon G . Developmentally regulated piRNA clusters implicate MILI in transposon control. Science. 2007; 316(5825):744-7. DOI: 10.1126/science.1142612. View

Carmell M, Girard A, van de Kant H, Bourchis D, Bestor T, de Rooij D . MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell. 2007; 12(4):503-14. DOI: 10.1016/j.devcel.2007.03.001. View

Reddien P, Oviedo N, Jennings J, Jenkin J, Sanchez Alvarado A . SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science. 2005; 310(5752):1327-30. DOI: 10.1126/science.1116110. View

Wang Y, Zayas R, Guo T, Newmark P . nanos function is essential for development and regeneration of planarian germ cells. Proc Natl Acad Sci U S A. 2007; 104(14):5901-6. PMC: 1851589. DOI: 10.1073/pnas.0609708104. View

Grivna S, Beyret E, Wang Z, Lin H . A novel class of small RNAs in mouse spermatogenic cells. Genes Dev. 2006; 20(13):1709-14. PMC: 1522066. DOI: 10.1101/gad.1434406. View

Tolia N, Joshua-Tor L . Slicer and the argonautes. Nat Chem Biol. 2006; 3(1):36-43. DOI: 10.1038/nchembio848. View

Guo T, Peters A, Newmark P . A Bruno-like gene is required for stem cell maintenance in planarians. Dev Cell. 2006; 11(2):159-69. DOI: 10.1016/j.devcel.2006.06.004. View

Lau N, Seto A, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel D . Characterization of the piRNA complex from rat testes. Science. 2006; 313(5785):363-7. DOI: 10.1126/science.1130164. View

Horwich M, Li C, Matranga C, Vagin V, Farley G, Wang P . The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr Biol. 2007; 17(14):1265-72. DOI: 10.1016/j.cub.2007.06.030. View

10.

Yin H, Lin H . An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature. 2007; 450(7167):304-8. DOI: 10.1038/nature06263. View

11.

Deng W, Lin H . miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell. 2002; 2(6):819-30. DOI: 10.1016/s1534-5807(02)00165-x. View

12.

Kirino Y, Mourelatos Z . Mouse Piwi-interacting RNAs are 2'-O-methylated at their 3' termini. Nat Struct Mol Biol. 2007; 14(4):347-8. DOI: 10.1038/nsmb1218. View

13.

Oviedo N, Levin M . smedinx-11 is a planarian stem cell gap junction gene required for regeneration and homeostasis. Development. 2007; 134(17):3121-31. DOI: 10.1242/dev.006635. View

14.

Newmark P, Reddien P, Cebria F, Sanchez Alvarado A . Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians. Proc Natl Acad Sci U S A. 2003; 100 Suppl 1:11861-5. PMC: 304099. DOI: 10.1073/pnas.1834205100. View

15.

Song J, Smith S, Hannon G, Joshua-Tor L . Crystal structure of Argonaute and its implications for RISC slicer activity. Science. 2004; 305(5689):1434-7. DOI: 10.1126/science.1102514. View

16.

Sanchez Alvarado A, Newmark P, Robb S, Juste R . The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration. Development. 2002; 129(24):5659-65. DOI: 10.1242/dev.00167. View

17.

Saito K, Sakaguchi Y, Suzuki T, Suzuki T, Siomi H, Siomi M . Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi- interacting RNAs at their 3' ends. Genes Dev. 2007; 21(13):1603-8. PMC: 1899469. DOI: 10.1101/gad.1563607. View

18.

Zayas R, Hernandez A, Habermann B, Wang Y, Stary J, Newmark P . The planarian Schmidtea mediterranea as a model for epigenetic germ cell specification: analysis of ESTs from the hermaphroditic strain. Proc Natl Acad Sci U S A. 2005; 102(51):18491-6. PMC: 1317986. DOI: 10.1073/pnas.0509507102. View

19.

Brennecke J, Aravin A, Stark A, Dus M, Kellis M, Sachidanandam R . Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. 2007; 128(6):1089-103. DOI: 10.1016/j.cell.2007.01.043. View

20.

Yeh R, Lim L, Burge C . Computational inference of homologous gene structures in the human genome. Genome Res. 2001; 11(5):803-16. PMC: 311055. DOI: 10.1101/gr.175701. View