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Maternally Inherited siRNAs Initiate piRNA Cluster Formation


Luo, Yicheng (2023) Maternally Inherited siRNAs Initiate piRNA Cluster Formation. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/f2nh-8w08.


PIWI-interacting RNAs (piRNAs) guide repression of transposable elements in germlines of animals to protect genome integrity. In Drosophila, the majority of piRNAs are produced from heterochromatic genomic loci, called piRNA clusters, that act as repositories of information about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, a complex specifically enriched on a dual-strand cluster, which is deposited on clusters guided by piRNAs, forming a feed-forward loop in which piRNAs promote their own biogenesis. However, this rises a fundamental question about how piRNA clusters are formed initially before cognate piRNAs are present.

Here we report the spontaneous de novo formation of a Rhino-dependent piRNA cluster from repetitive transgenic sequences. We show that cluster formation occurs gradually over several generations and requires continuous trans-generational transmission of small RNAs from mothers to their progeny. Importantly, we discovered that maternally-supplied siRNAs are responsible for triggering de novo cluster activation in progeny. In contrast, the siRNA pathway is dispensable for piRNA cluster function and maintenance after its establishment. These results revealed an unexpected cross-talk between the siRNA and piRNA pathways and suggested a mechanism for de novo formation of piRNA clusters triggered by production of siRNAs.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:(Genetics) ; piRNA siRNA
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Aravin, Alexei A.
Thesis Committee:
  • Guttman, Mitchell (chair)
  • Shan, Shu-ou
  • Gradinaru, Viviana
  • Aravin, Alexei A.
Defense Date:29 September 2022
Record Number:CaltechTHESIS:11042022-055503832
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Ch. 2
Luo, Yicheng0000-0003-3704-2389
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15058
Deposited By: Yicheng Luo
Deposited On:30 Nov 2022 22:25
Last Modified:08 Nov 2023 00:09

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