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An intron-based timer for circadian rhythms.

Ye Yuan1, Amanda Linskens1, Rafael De Gouvea2

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This summary is machine-generated.

A novel RNA timer in the Drosophila timeless (tim) gene, intron P, controls circadian rhythms by regulating mRNA nuclear retention. This intron

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • RNA Biology

Background:

  • Circadian clocks govern ~24-hour rhythms in eukaryotes via transcriptional-translational feedback loops.
  • The precise molecular mechanisms setting the circadian period remain incompletely understood.

Purpose of the Study:

  • To identify novel molecular timers regulating circadian period length.
  • To investigate the role of RNA processing in circadian gene expression.

Main Methods:

  • Single-molecule imaging
  • Nascent RNA sequencing
  • CRISPR-mediated gene editing
  • Heterologous reporter assays in Drosophila and human cells

Main Results:

  • A single intron (intron P) in the Drosophila timeless (tim) gene acts as an RNA-based molecular timer.
  • Intron P causes nuclear retention of ~50% of tim mRNAs due to inefficient splicing, controlling period length.
  • Removal of intron P shortens the circadian period to ~22 hours; its insertion into other genes confers nuclear retention.
  • RNA-binding proteins (Hrb27C, Squid, Qkr58E-2) modulate intron P splicing kinetics.

Conclusions:

  • tim intron P is the first identified intron-based molecular timer in circadian clocks.
  • Splicing kinetics represent a critical regulatory layer in temporal gene expression.
  • This mechanism has potential implications for development and immunity.