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Lint-O cooperates with L(3)mbt in target gene suppression to maintain homeostasis in fly ovary and brain

Hitomi Yamamoto-Matsuda1, Keita Miyoshi2,3, Mai Moritoh1

  • 1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.

EMBO Reports
|August 22, 2022
PubMed

Insights

Loss of lethal(3)malignant brain tumor [l(3)mbt] protein causes ovarian dysfunction and brain tumors by disrupting piRNA amplification. A novel co-regulator, Lint-O, works with l(3)mbt to suppress these genes.

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Loss-of-function mutations in Drosophila lethal(3)malignant brain tumor [l(3)mbt] lead to ectopic germline gene expression and brain tumors.
  • L(3)mbt loss in ovarian somatic cells (OSCs) causes aberrant piRNA amplification and infertility, but the mechanism is unknown.

Purpose of the Study:

  • To elucidate the mechanism by which L(3)mbt regulates piRNA pathway genes in Drosophila ovarian somatic cells.
  • To identify novel co-regulators of L(3)mbt involved in maintaining cellular homeostasis.

Main Methods:

  • Chromatin immunoprecipitation sequencing (ChIP-seq) to map L(3)mbt genomic binding in OSCs.
  • RNA sequencing (RNA-seq) to analyze gene expression changes upon L(3)mbt depletion.
  • Co-immunoprecipitation and mass spectrometry to identify L(3)mbt interactors.

Main Results:

  • L(3)mbt genomic binding does not always correlate with gene regulation; it controls piRNA pathway genes through multiple mechanisms.
  • A novel L(3)mbt co-regulator, "L(3)mbt interactor in OSCs" (Lint-O), was identified.
  • Lint-O binds to piRNA amplifier genes similarly to L(3)mbt, and its loss phenocopies L(3)mbt loss, causing female sterility and tumorous brains.

Conclusions:

  • L(3)mbt and its novel co-suppressor Lint-O collaborate to suppress target genes, maintaining ovarian and brain homeostasis.
  • The L(3)mbt-Lint-O complex is crucial for preventing ectopic piRNA amplification and associated pathologies.
Keywords:
L(3)mbtLint-Ofertilitygene regulationpiRNA

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