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RNA Biology Section

About Our Research

The Haase group investigates the ongoing conflict between mobile genetic parasites and their host genome by understanding how PIWI-interacting RNAs (piRNAs) are generated and specifically silence transposons. The intrinsic ability of transposons to amplify and reinsert into novel genomic locations resulted in their colonization of half of our genome. Their activity threatens genome integrity and must be restrained. PiRNAs and their PIWI protein partners, establish transposon silencing in germ cells, thus securing the survival of a species. While recent advances have deciphered the framework of piRNA-mediated transposon control, molecular events that ensure specificity and efficiency of the pathway remain largely unknown. Our current projects focus on three distinct aspect of piRNA biology through an integrative approach combining biochemistry, fly genetics, and genomics:

  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

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)

Model for the establishment of a 1U-bias. Our data support that the 1U-bias is established in two steps by differential gating against all nucleotides but Uridine. First, purines (A/G) are reduced during piRNA biogenesis in an SL-independent manner. Consecutively, 1C is discriminated against upon piRISC formation by interactions with Piwi’s SL.

Photo of a simplified model of mammalian piRNA pathways highlighting conserved piRNA biogenesis factors.
Mammalian piRNA pathways (from: Genzor et al., PNAS 2019).

A simplified model of mammalian piRNA pathways highlighting conserved piRNA biogenesis factors.

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). 

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 (Pane A. et al., Dev Cell 2007), 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 (Stein, Genzor, Mitra, Elchert et al., Nat Commun. 2019)