Piwi-interacting RNA
[7] They are distinct from microRNA (miRNA) in size (26–31 nucleotides as opposed to 21–24 nt), lack of sequence conservation, increased complexity, and independence of Dicer for biogenesis, at least in animals.
[11] piRNAs have been identified in both vertebrates and invertebrates, and although biogenesis and modes of action do vary somewhat between species, a number of features are conserved.
piRNAs in Caenorhabditis elegans have a 5’ monophosphate and a 3’ modification that acts to block either the 2’ or 3’ oxygen;[13] this has also been confirmed to exist in Drosophila melanogaster,[14] zebrafish,[15] mice,[16] and rats.
[19] In the early 1980s, it was discovered that a single mutation in the fruit fly genome could specifically activate all copies of a retrovirus-like element called Gypsy in the female germline.
[10] Sequencing of the 200,000-bp flamenco locus was difficult, as it turned out to be packed with transposable element fragments (104 insertions of 42 different transposons, including multiple Gypsies), all facing the same direction.
[31][32] Also proposed is a ‘Ping Pong’ mechanism wherein primary piRNAs recognise their complementary targets and cause the recruitment of piwi proteins.
[19] A significant number of piRNAs identified in zebrafish and D. melanogaster contain adenine at their tenth position,[11] and this has been interpreted as possible evidence of a conserved biosynthetic mechanism across species.
[32][34] This relationship is known as the "ping-pong signature" and is also observed in associated piRNA from Mili and Miwi2 proteins isolated from mouse testes.
The proposed function of Ping-Pong in Drosophila or in mouse remains to be understood, but a leading hypothesis is that the interaction between Aub and Ago3 allows for a cyclic refinement of piRNA that are best suited to target active transposon sequences.
Conversely, Ago3 piRNA sequences are predominantly of sense orientation to transposable element transcripts and are derived from the product of Aub cleavage of transposon mRNA.
In this way, the Aub or Ago3 'responder' piRNA sequence cleaves a complementary target that is then sliced at periodic intervals of approximately 27 nucleotides that are sequentially loaded into Piwi protein.
[11][31] Transposons have a high potential to cause deleterious effects on their hosts[21] and, in fact, mutations in piRNA pathways have been found to reduce fertility in D.
[20] Further, it is thought that piRNA and endogenous small interfering RNA (endo-siRNA) may have comparable and even redundant functionality in transposon control in mammalian oocytes.
[22] piRNAs appear to affect particular methyltransferases that perform the methylations which are required to recognise and silence transposons,[31] but this relationship is not well understood.
In Dipterans viral-derived piRNAs derived from positive-sense RNA viruses were first identified in Drosophila ovarian somatic sheet (OSS) cells.
[45] Subsequent experimental studies have demonstrated that the piRNA pathway is not required for antiviral defence in Drosophila melanogaster.
[18] Genetic screens examining fertility defects identified a number of proteins that are not Piwi-clade Argonautes, yet produce the same sterility phenotypes as Piwi mutants.
Many factors required for the piRNA pathway in Drosophila contain Tudor domains that are known to bind symmetrically dimethylated arginine residues (sDMA) present in methylation motifs of Piwi proteins.
