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Gene Review

PIWIL1  -  piwi-like RNA-mediated gene silencing 1

Homo sapiens

Synonyms: CT80.1, HIWI, MIWI, PIWI, Piwi-like protein 1
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Disease relevance of PIWIL1

  • Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas [1].
  • Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells [2].
  • We found that the expression ratio of hiwi in normal gastric tissues, atrophic gastritis, intestinal metaplasia and gastric cancers was 10% (5/50), 36% (18/50), 36% (18/50) and 76% (38/50), respectively, which was consistent with precancerous development [2].

High impact information on PIWIL1

  • Recently, the members of the Piwi sub-family have been shown to interact with new classes of short regulatory RNAs, Piwi-interacting RNAs (piRNAs) and repeat-associated small interfering RNAs (rasiRNAs), which has implications for developmental processes and introduces a new dimension to the field of RNA silencing [3].
  • We previously reported that MIWI, a murine PIWI family member, is required for initiating spermiogenesis, a process that transforms round spermatids into mature sperm [4].
  • Particularly, microRNA (miRNA)-mediated translational repression involving PIWI/Argonaute family proteins has been widely recognized as a novel mechanism of gene regulation [4].
  • Both, mouse and human Piwil2 genes, members of the piwi gene family, are specifically expressed in testis [5].
  • Placing CD34(+) cells into culture conditions that supported differentiation and rapid exit from the stem cell compartment resulted in a loss of hiwi expression by day 5 of a 14-day culture period [6].

Biological context of PIWIL1


Anatomical context of PIWIL1

  • Thus, hiwi is specifically expressed in both normal and malignant spermatogenic cells in a maturation stage-dependent pattern, in which it might function in germ cell proliferation [1].
  • In addition, gain of this chromosomal region has been found in some TGCTs. hiwi encodes a 3.6 kb mRNA that is expressed abundantly in the adult testis [1].
  • In contrast, deletion of the Piwi domain led to a loss of siRNAs but did not abolish polyribosome association [7].

Associations of PIWIL1 with chemical compounds


Other interactions of PIWIL1

  • Both roles appear to be widespread among living eukaryotes and this diversification of function could account for the evolutionary conservation of duplicated Argonaute-Piwi proteins [8].
  • These studies suggest that hiwi maybe an important negative developmental regulator, which, in part, underlies the unique biologic properties associated with hematopoietic stem and progenitor cells [6].
  • The PIWI domain, a highly conserved motif within Argonaute, has been shown to adopt an RNase H fold critical for the endonuclease cleavage activity of RISC [9].

Analytical, diagnostic and therapeutic context of PIWIL1

  • RT-PCR findings demonstrated that hiwi was expressed in different gastric cancer cell lines [2].
  • To identify the HIWI protein in gastric cancer, we developed a specific monoclonal antibody against HIWI and immunohistochemistry was performed on various gastric tissues [2].
  • For example, African "Pygmies," Philippine "Negritos," and the Hiwi of Venezuela are characterized by relatively fast child-juvenile growth for their adult body size (used as a proxy for energetic availability) [10].


  1. Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Qiao, D., Zeeman, A.M., Deng, W., Looijenga, L.H., Lin, H. Oncogene (2002) [Pubmed]
  2. Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells. Liu, X., Sun, Y., Guo, J., Ma, H., Li, J., Dong, B., Jin, G., Zhang, J., Wu, J., Meng, L., Shou, C. Int. J. Cancer (2006) [Pubmed]
  3. Argonaute: a scaffold for the function of short regulatory RNAs. Parker, J.S., Barford, D. Trends Biochem. Sci. (2006) [Pubmed]
  4. MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Grivna, S.T., Pyhtila, B., Lin, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Lee, J.H., Schütte, D., Wulf, G., Füzesi, L., Radzun, H.J., Schweyer, S., Engel, W., Nayernia, K. Hum. Mol. Genet. (2006) [Pubmed]
  6. Human CD34(+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Sharma, A.K., Nelson, M.C., Brandt, J.E., Wessman, M., Mahmud, N., Weller, K.P., Hoffman, R. Blood (2001) [Pubmed]
  7. Function of the Trypanosome Argonaute 1 protein in RNA interference requires the N-terminal RGG domain and arginine 735 in the Piwi domain. Shi, H., Ullu, E., Tschudi, C. J. Biol. Chem. (2004) [Pubmed]
  8. On the origin and functions of RNA-mediated silencing: from protists to man. Cerutti, H., Casas-Mollano, J.A. Curr. Genet. (2006) [Pubmed]
  9. Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Ma, J.B., Yuan, Y.R., Meister, G., Pei, Y., Tuschl, T., Patel, D.J. Nature (2005) [Pubmed]
  10. Growth rates and life histories in twenty-two small-scale societies. Walker, R., Gurven, M., Hill, K., Migliano, A., Chagnon, N., De Souza, R., Djurovic, G., Hames, R., Hurtado, A.M., Kaplan, H., Kramer, K., Oliver, W.J., Valeggia, C., Yamauchi, T. Am. J. Hum. Biol. (2006) [Pubmed]
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