RNA Biology Section

Small RNA guardians of genome integrity.

We aim to understand how small non-coding RNAs guard genomic integrity.

piRNA pathways Genome surveillance Interdisciplinary genetics Bethesda, MD
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Mission & approach

Research Goal

We aim to understand how small non-coding RNAs guard genomic integrity.


Current Focus

Small non-coding RNAs play vital roles in development and disease by regulating gene expression, defending against viruses, and silencing mobile genetic elements (transposons). Our research focuses on PIWI-interacting RNAs (piRNAs), which safeguard genome integrity and are essential for germ cell health and fertility. To unravel the molecular mechanisms of this RNA-based immune system, we integrate genetics, genomics, and biochemistry. These studies deepen our understanding of the fundamental processes protecting genome integrity in animals and humans and inform molecular strategies for technological and therapeutic advances.

Why it matters

Maintaining genome stability is essential for cellular and organismal health, as its disruption is linked to diseases including infertility, inflammation, and cancer. Understanding RNA-guided genome protection opens paths for advancing fertility treatments and developing biomedical strategies to counteract genomic instability in disease.

In plain language

Genomes serve as life’s instruction manuals, guiding cell, tissue, and organ formation. Protecting their integrity is crucial for fertility and species survival. Our research focuses on specialized molecular guardians that safeguard germ cell genomes in animals and humans. By uncovering these protective mechanisms, we aim to strengthen our understanding of genome stability and develop new diagnostic and therapeutic strategies.

Future directions

Small RNA-guided molecular machines are found across all domains of life, yet we are only beginning to understand their diverse roles in gene regulation and genome surveillance. Unraveling these pathways is essential for elucidating their functions in health and disease and will continue to expand the molecular toolkit for research and therapeutic applications.

Selected publications

  • Pachytene piRNAs define a conserved program of meiotic gene regulation
    Loubalova Z., Ahrend, F., Stoyko, D., Cosby, R., Ralls, S., Meister, G., Macfarlan, T., Haase, A.D. bioRxiv
  • Protocol for assembling, prioritizing, and characterizing piRNA clusters using the piRNA Cluster Builder
    Ahrend F., Konstantinidou P., Loubalova Z., Wang Y., Lorenzi H., Meister G., Macfarlan T., Haase A.D. Cell STAR Protocols
  • A comparative roadmap of PIWI-interacting RNAs across seven species reveals insights into de novo piRNA-precursor formation in mammals.
    Konstantinidou P, Loubalova Z, Ahrend F, Friman A, Almeida MV, Poulet A, Horvat F, Wang Y, Losert W, Lorenzi H, Svoboda P, Miska EA, van Wolfswinkel JC, Haase AD. Cell Rep. 2024;43(10):114777.
  • Hierarchical length and sequence preferences establish a single major piRNA 3'-end.
    Stoyko D, Genzor P, Haase AD. iScience. 2022;25(6):104427.
  • Functional editing of endogenous genes through rapid selection of cell pools (Rapid generation of endogenously tagged genes in Drosophila ovarian somatic sheath cells).
    Meng Q, Stoyko D, Andrews CM, Konstantinidou P, Genzor P, O T, Elchert AR, Benner L, Sobti S, Katz EY, Haase AD. Nucleic Acids Res. 2022;50(15):e90.
  • Cellular abundance shapes function in piRNA-guided genome defense.
    Genzor P, Konstantinidou P, Stoyko D, Manzourolajdad A, Marlin Andrews C, Elchert AR, Stathopoulos C, Haase AD. Genome Res. 2021;31(11):2058-2068.
  • Decoding the 5' nucleotide bias of PIWI-interacting RNAs.
    Stein CB, Genzor P, Mitra S, Elchert AR, Ipsaro JJ, Benner L, Sobti S, Su Y, Hammell M, Joshua-Tor L, Haase AD. Nat Commun. 2019;10(1):828.
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