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RNA Biology Section

About Our Research

The Haase group investigates the ongoing struggle between mobile genetic elements and their host genome by exploring how PIWI-interacting RNAs (piRNAs) are generated and utilized to specifically silence transposons. Due to the inherent capacity of transposons to mobilize, amplify and insert into new genomic locations, they have colonized around half of our genome. Their activity poses a threat to genome integrity and therefore needs to be controlled. In germ cells, piRNAs and their PIWI protein partners establish transposon silencing, thereby securing species survival. Although recent progress has uncovered the fundamental framework of piRNA-mediated transposon control, the molecular mechanisms that guarantee the pathway's specificity and effectiveness remain largely unknown. Our present research projects take an integrative approach, utilizing biochemistry, genetics, and genomics, to concentrate on three distinct aspects of piRNA biology:

  1. Identify mechanisms that designate transcripts for processing into piRNAs.
  2. Determine rules that govern robustness and adaptability of piRNA-mediated transposon control.
  3. Establish a robust system to study human piRNA biology and its potential impact on genome stability in disease.

Research Images

Hierarchical length and sequence preferences establish a single major piRNA 3′-end
Hierarchical length and sequence preferences establish a single major piRNA 3′-end’ (Stoyko et al., iScience 2022)
Cellular abundance shapes function in piRNA-guided genome defense
Cellular abundance shapes function in piRNA-guided genome defense’ (Genzor*, Konstantinidou*, Stoyko*, et al., Genome Research 2021)
Functional editing of endogenous genes through rapid selection of cell pools
Functional editing of endogenous genes through rapid selection of cell pools’ (Meng*, Stoyko*, Marlin Andrews*, et al., NAR 2022; and Stoyko et al., Curr Protoc. 2022)
Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells
Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells’ (Genzor et al., PNAS 2019)
Decoding the 5 nucleotide bias of PIWI-interacting RNAs
Decoding the 5' nucleotide bias of PIWI-interacting RNAs’ (Stein*, Genzor*, Mitra* et al., Nat Commun. 2019)
An oversimplified depiction of the three major small RNA pathways in animals
An oversimplified depiction of the three major small RNA pathways in animals.’ (Review, RNA Biology 2023)
PiRNA biogenesis in flies and mice
PiRNA biogenesis in flies and mice.’ (Review, RNA Biology 2023)
Photo of model for the establishment of a 1U-bias. The 1U-bias is established by differential gating against all nucleotides but Uridine (U).
PiRNAs like to be with 'U': The 1U-bias is established by differential gating against all nucleotides but Uridine (U) (from: Stein*, Genzor*, Mitra*, Elchert* et al., Nat Commun. 2019)
Photo of a simplified model of mammalian piRNA pathways highlighting conserved piRNA biogenesis factors.
Mammalian piRNA pathways (from: Genzor et al., PNAS 2019).
Photo of the mouse homolog of Drosophila zucchini (zuc), mmZuc/PLD6, is a novel single-strand-specific endonuclease. Zuc, originally identified by Trudi Schupbach and implicated in piRNA-silencing by her group, is a key-enzyme in piRNA biogenesis. Zuc generates the diagnostic 5’ monophosphorylated ends of primary piRNAs, and in select cases also their mature 3’ termini. Sequence preferences of the Zuc processor complex contribute to the 1U-bias of Piwi-piRNAs
The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis (adapted from: Ipsaro*, Haase* et al., Nature 2012).