About piRNA
  • 1
  • 1998-12
  • Discovery of Piwi
  • Piwi gene was firstly cloned and characterized in Drosophila, and it showed that piwi is required
    for the asymmetric division of germ-line stem cells. Piwi encodes a highly basic protein which is well conserved
    during evolution.

    A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal,Genes Dev.1998;
    12(23): 3715-3727

  • 2
  • 2006-07
  • Discovery of piRNA
  • Girard, A. and Aravin, A. described a new class of small RNA that bind to MILI or MIWI(murine Piwi
    protein) in mouse male germ cells, they referred to them as Piwi-interacting RNA(piRNA). piRNAs
    are 26-31nt in length and share a strong preference for a 5’ uridine. Genomic mapping of piRNAs
    reveals a limited number of clusters, wherein long stretches of piRNAs are derived from only one
    strand. Similar piRNAs can also be found in rat and human, and the major clusters occurring in or-
    thologous chromosomal regions.

    A germline-specific class of small RNAs binds mammalian Piwi proteins,Nature 2006;442(7099):199-202
    A novel class of small RNAs bind to MILI protein in mouse testes, Naure 2006;442(7099):203-207
    A novel class of small RNAs in mouse spermatogenic cells, Genes Dev 2006;20(13):1709-14

  • 3
  • 2007-04
  • Post-transcriptional silencing of transposons
  • Alexei A. Aravin discovered that the most abundant class of mouse prepachytene piRNAs are 
    generated from transposon-rich regions of the genome, it suggested that piRNAs function in
    transposon silencing.

    Developmentally regulated piRNA clusters implicate MILI in transposon control, Science 2007;316(5828):744-747

  • 4
  • 2008
  • DNA methylation of transposons
  • Mice lacking one or more of their piwi homologs were found to have substantial demethylation and
    derepression of transposable elements, it pointed toward a role for piRNAs in maintaining germline
    genome integrity and transposon control throught de novo DNA methylation.

    A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 2008;31(6), 785–799
    An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 2008;322(5906), 1387–1392
    DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes
    Dev. 2008;22(7), 908–917

  • 5
  • 2010-10
  • Post-transcriptional gene silencing
  • it has been discovered that a few piRNA derive from individual mRNA transcripts, and could participate
    in ping-pong mechanism to generate secondary piRNAs.

    A single female-specific piRNA is the primary determiner of sex in the silkworm Nature 2014;509:633-636

  • 6
  • 2012-04
  • DNA methylation of genes
  • Priyamvada found piRNA have a critical role in the epigenetic regulation of CREB2 promoter.Expos-
    ure to serotonin causes a significant but delayed upregulation of the neuronally enriched piRNA piR-F,
    which recruits the piwi/piRNA complex to bind a target site on the nascent transcript in the 5'UTR of
    CREB2 pre-mRNA by putative sequence-specific direction. This leads to the recruitment of factors that
    promote the activation of DNMT, a DNA methyltransferase. DNMT acts to methylate the proximal (but
    not the distal) CpG island in the CREB2 promoter, leading to reduced expression of CREB2, induction of
    long-term facilitation, and formation of memory.

    A Role for Neuronal piRNAs in the Epigenetic Control of Memory-Related Synaptic Plasticity Cell 2008;149(3):694-707

  • 7
  • 2014-06
  • H3K9me3 mark establishment
  • Dubravka Pezic found transcripts from a full-length LINE in the nucleus of embryonic prospermatogonia
    are recognized by a MIWI2–piRNA complex, which recruits a histone methyltransferase (HMTase). This
    results in deposition of the H3K9me3 mark on LINE 5’repeats and in the adjacent upstream region. The
    piRNA associates only with transcripts from actively transcribed copies of TEs. Truncated copies, which
    are not transcribed, are not targeted by piRNAs.

    piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells Genes & Development

  • 8
  • 2015-05
  • piRNA biogenesis
  • Mohn, F., D. Handler, and J. Brennecke show that primary piRNA biogenesis is initiated by secondary
    piRNA-guided transcript cleavage and Zucchini plays a central role in defining piRNA 5' and 3' ends.
    Han, B.W., et al. report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate
    primary piRNA production from cleaved transposon RNAs.

    Noncoding RNA. piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis.
    Science. 2015 May 15;348(6236):812-817. doi: 10.1126/science.aaa1039.
    Noncoding RNA. piRNA-guided transposon cleavage initiates Zucchini-dependent, phased piRNA production.
    Science. 2015 May 15;348(6236):817-21. doi: 10.1126/science.aaa1264.

  • 9
  • 2017-06
  • Piwi/piRNA and male infertility
  • MIWI binds the histone ubiquitin ligase RNF8 in a piRNA-independent manner, and MIWI stabilization
    sequesters RNF8 in the cytoplasm of late spermatids. The resulting aberrant sperm show histone retention,
    abnormal morphology, and severely compromised activity, which can be functionally rescued via blocking
    RNF8-MIWI interaction in spermatids with an RNF8-N peptide. The findings identify Piwi as a factor in
    human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.

    Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine
    Exchange during Spermiogenesis.Cell. 2017 Jun 1;169(6):1090-1104.e13. doi: 10.1016/j.cell.2017.04.034.

  • 10
  • 2017-09
  • piRNA and heterochromatin
  • In Drosophila, transcription of piRNA clusters is enforced through RNA polymerase II pre-initiation complex
    formation within repressive heterochromatin. This is accomplished through Moonshiner which is recruited
    to piRNA clusters via the heterochromatin protein-1 variant Rhino. Moonshiner triggers transcription initiation
    within piRNA clusters by recruiting the TATA-box binding protein (TBP)-related factor TRF2. Transcription of
    heterochromatic small RNA source loci relies on direct recruitment of the core transcriptional machinery to
    DNA via histone marks rather than sequence motifs.

    A heterochromatin-dependent transcription machinery drives piRNA expression.Nature. 2017 Sep 7;549(7670):54-59.
    doi: 10.1038/nature23482.

  • 11
  • 2017-12
  • piRNA and splicing
  • Teixeira FK et al show that splicing regulation is mechanistically achieved together with piRNA-mediated changes
    to repressive chromatin states, and relies on the function of the Piwi-piRNA complex proteins Asterix (also known
    as Gtsf1) and Panoramix (Silencio), as well as Heterochromatin protein 1a (HP1a; encoded by Su(var)205) in Drosophila.

    piRNA-mediated regulation of transposon alternative splicing in the soma and germ line.Nature. 2017 Dec 14;552(7684):268-272.
    doi: 10.1038/nature25018.

  • 12
  • 2018-02
  • piRNA targeting rules
  • Zhang D. et al show that piRNA targeting in Caenorhabditis elegans can tolerate a few mismatches but prefer
    perfect pairing at the seed region. The broad targeting capacity of piRNAs underlies the germline silencing
    of transgenes in C. elegans Transgenes engineered to avoid piRNA recognition are stably expressed. Many
    endogenous germline-expressed genes also contain predicted piRNA targeting sites, and periodic An/Tn clusters
    (PATCs) are an intrinsic signal that provides resistance to piRNA silencing.

    The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes.Science. 2018 Feb 2;359(6375):587-592.
    doi: 10.1126/science.aao2840.