Piwi

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Piwi domain
Structure of the Pyrococcus furiosus Argonaute protein.[1]
Identifiers
SymbolPiwi
PfamPF02171
InterProIPR003165
PROSITEPS50822
CDDcd02826
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1u04​, 1w9h​, 1ytu​, 1yvu​, 1z25​, 1z26​, 2bgg​, 2f8s​, 2f8t​, 2nub​, 2w42
siRNA, components of the RNA-induced silencing complex that mediates gene silencing by RNA interference
.
All human Piwi proteins and argonaute proteins have the same RNA binding domains, PAZ and Piwi.[2]
Piwi-piRNA interactions: Within the nucleus, this pathway is involved in DNA methylation (A), histone methylation of H3K9 through interactions with heterochromatin protein 1 (HP1) and H3K9 histone methyltransferase (B). The Piwi-piRNA pathway also interacts with the elF translational initiator (C).[3]

Piwi (or PIWI)

conserved RNA-binding proteins and are present in both plants and animals.[7] Piwi proteins belong to the Argonaute/Piwi family and have been classified as nuclear proteins. Studies on Drosophila have also indicated that Piwi proteins have no slicer activity conferred by the presence of the Piwi domain.[8] In addition, Piwi associates with heterochromatin protein 1
, an epigenetic modifier, and piRNA-complementary sequences. These are indications of the role Piwi plays in epigenetic regulation. Piwi proteins are also thought to control the biogenesis of piRNA as many Piwi-like proteins contain slicer activity which would allow Piwi proteins to process precursor piRNA into mature piRNA.

Protein structure and function

The structure of several Piwi and Argonaute proteins (Ago) have been solved. Piwi proteins are RNA-binding proteins with 2 or 3 domains: The N-terminal PAZ domain binds the 3'-end of the guide RNA; the middle MID domain binds the 5'-phosphate of RNA; and the C-terminal PIWI domain acts as an RNase H endonuclease that can cleave RNA.[9][10] The small RNA partners of Ago proteins are microRNAs (miRNAs). Ago proteins utilize miRNAs to silence genes post-transcriptionally or use small-interfering RNAs (siRNAs) in both transcription and post-transcription silencing mechanisms. Piwi proteins interact with piRNAs (28–33 nucleotides) that are longer than miRNAs and siRNAs (~20 nucleotides), suggesting that their functions are distinct from those of Ago proteins.[9]

Human Piwi proteins

Presently there are four known human Piwi proteins—PIWI-like protein 1, PIWI-like protein 2, PIWI-like protein 3 and PIWI-like protein 4. Human Piwi proteins all contain two RNA binding domains, PAZ and Piwi. The four PIWI-like proteins have a spacious binding site within the PAZ domain which allows them to bind the bulky 2’-OCH3 at the 3’ end of piwi-interacting RNA.[11]

One of the major human

tumours such as seminomas, is called hiwi (for human piwi).[12]

Homologous proteins in mice have been called miwi (for mouse piwi).[13]

Role in germline cells

PIWI proteins play a crucial role in fertility and germline development across animals and ciliates. Recently identified as a polar granule component, PIWI proteins appear to control germ cell formation so much so that in the absence of PIWI proteins there is a significant decrease in germ cell formation. Similar observations were made with the mouse homologs of PIWI, MILI, MIWI and MIWI2. These homologs are known to be present in spermatogenesis. Miwi is expressed in various stages of spermatocyte formation and spermatid elongation where Miwi2 is expressed in

Sertoli cells. Mice deficient in either Mili or Miwi-2 have experienced spermatogenic stem cell arrest and those lacking Miwi-2 underwent a degradation of spermatogonia.[14]
The effects of piwi proteins in human and mouse germlines seems to stem from their involvement in translation control as Piwi and the small noncoding RNA, piwi-interacting RNA (piRNA), have been known to co-fractionate polysomes. The piwi-piRNA pathway also induces thus affecting transcription. The piwi-piRNA pathway also appears to protect the genome. First observed in Drosophila, mutant piwi-piRNA pathways led to a direct increase in dsDNA breaks in ovarian germ cells. The role of the piwi-piRNA pathway in transposon silencing may be responsible for the reduction in dsDNA breaks in germ cells.

Role in RNA interference

The piwi domain

base stacking-interactions between the base and neighbouring tyrosine residues.[17]

Recent evidence suggests that the functional role of piwi proteins in germ-line determination is due to their capacity to interact with miRNAs. Components of the miRNA pathway appear to be present in pole plasm and to play a key role in early development and morphogenesis of Drosophila melanogaster embryos, in which germ-line maintenance has been extensively studied.[18]

piRNAs and transposon silencing

A novel class of longer-than-average miRNAs known as

rasiRNAs).[22]

Although their biogenesis is not yet well understood, piRNAs and Piwi proteins are thought to form an endogenous system for silencing the expression of

selfish genetic elements such as retrotransposons and thus preventing the gene products of such sequences from interfering with germ cell formation.[21][23]

Footnotes

  1. ^ The word Wimpy itself comes from White color of eyes and Impotency [or profound infertility]. Y is added as a suffix to form a more pronounceable and coherent word.[5]

References

External links

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