PIWI-interacting RNAs: small RNAs with big functions

  title={PIWI-interacting RNAs: small RNAs with big functions},
  author={Deniz M. Ozata and Ildar V Gainetdinov and Ansgar Zoch and D{\'o}nal O’Carroll and Phillip D. Zamore},
  journal={Nature Reviews Genetics},
In animals, PIWI-interacting RNAs (piRNAs) of 21–35 nucleotides in length silence transposable elements, regulate gene expression and fight viral infection. piRNAs guide PIWI proteins to cleave target RNA, promote heterochromatin assembly and methylate DNA. The architecture of the piRNA pathway allows it both to provide adaptive, sequence-based immunity to rapidly evolving viruses and transposons and to regulate conserved host genes. piRNAs silence transposons in the germ line of most animals… 

Comparative analysis of piRNA sequences, targets and functions in nematodes

This work characterized the piRNA pathway in C. briggsae and identified a set of protein-coding genes that are evolutionarily conserved piRNA targets, and found that transcripts with few introns are prone to small RNA overamplification.

An introduction to PIWI-interacting RNAs (piRNAs) in the context of metazoan small RNA silencing pathways

This review aims to introduce principles of piRNA silencing in the context of metazoan small RNA pathways and identify novel nucleases, helicases and RNA binding proteins identified in piRNA biology.

Emerging roles and functional mechanisms of PIWI-interacting RNAs.

The most recent advances in the understanding of piRNA biogenesis, the molecular mechanisms of pi RNA function and the emerging roles of piRNAs in germ line development mainly in flies and mice, and in infertility, cancer and neurological diseases in humans are discussed.

Conserved Small Nucleotidic Elements at the Origin of Concerted piRNA Biogenesis from Genes and lncRNAs

A new type of a conserved regulatory pathway is brought to light, the snetDNA-pathway, by which short sequences can include independent genes and lncRNAs in the same biological pathway, suggesting that such regulation networks are recurrent, possibly conserved, in evolutionary history.

A pathway to produce non-coding piRNAs from endogenous protein-coding regions supports Drosophila spermatogenesis

The data highlight that Drosophila testes employ a unique strategy to expand the diversity of germline piRNAs supporting late spermatogenesis, and provide evidence that Ago2-bound short interfering (si)RNAs and micro(mi) RNAs specify precursors and direct endo-piRNA biogenesis.

Structural basis for piRNA targeting.

Cryo-electron microscopy structures of a PIWI-piRNA complex from the sponge Ephydatia fluviatilis with and without target RNAs are presented, and a biochemical analysis of target recognition is presented, making piRNAs less promiscuous than miRNAs.

Primate piRNA Cluster Evolution Suggests Limited Relevance of Pseudogenes in piRNA-Mediated Gene Regulation

It is shown that pseudogenes in reserve orientation relative to piRNA cluster transcription direction generally do not exhibit signs of selection pressure and cause weakly conserved targeting of homologous genes among species, suggesting a lack of functional constraints and thus only a minor significance for gene regulation in most cases.

GTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins

GTSF1 potentiates the weak, intrinsic, piRNA-directed RNA cleavage activities of PIWI proteins, transforming them into efficient endoribonucleases, and is thus an example of an auxiliary protein that potentiate the catalytic activity of an Argonaute protein.

Genetic polymorphisms lead to major, locus-specific, variation in piRNA production in mouse

The sequencing and analysis of small RNAs from the mouse male germline of four classical inbred strains, one inbred wild-derived strain and one outbred strain are reported, finding that genetic differences between individuals underlie variation in piRNA expression.



Function, Targets, and Evolution of Caenorhabditis elegans piRNAs

It is demonstrated that Caenorhabditis elegansPiRNAs provide heritable, sequence-specific triggers for RNA interference in C. elegans, and the data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements.

The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes

It is shown that piRNA targeting in Caenorhabditis elegans can tolerate a few mismatches but prefer perfect pairing at the seed region, and highlights a distinct strategy that C. elegans uses to distinguish endogenous from foreign nucleic acids.

piRNA-guided slicing specifies transcripts for Zucchini-dependent, phased piRNA biogenesis

The data uncover an evolutionarily conserved piRNA biogenesis mechanism in which Zucchini plays a central role in defining piRNA 5′ and 3′ ends, potentially helping them to target endogenous and novel transposons more effectively.

Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice

TDRD12 is identified as a unique piRNA biogenesis factor in mice and its importance for transposon silencing is demonstrated and a role for the multidomain protein in mediating complex formation with other participants during secondary pi RNA biogenesis is suggested.

Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements

It is reported that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago, calling into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrating that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropods evolution.

Panoramix enforces piRNA-dependent cotranscriptional silencing

The CG9754 protein is a component of Piwi complexes that functions downstream of PiWI and its binding partner, Asterix, in transcriptional silencing, and it is proposed that this protein could act as an adaptor, scaffolding interactions between the piRNA pathway and the general silencing machinery that it recruits to enforce transcriptional repression.