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Non-coding Y RNAs associate with early replicating euchromatin in concordance with the origin recognition complex.

Eyemen Kheir1, Torsten Krude2

  • 1Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.

Journal of Cell Science
|February 26, 2017
PubMed
Summary

Non-coding Y RNAs are crucial for DNA replication initiation. Their association with chromatin changes during the cell cycle, particularly in S phase, suggesting a functional role alongside the origin recognition complex (ORC).

Keywords:
Cell cycleChromatin associationDNA replicationInitiationNon-coding Y RNAORCOrigin recognition complex

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Non-coding Y RNAs are vital for initiating chromosomal DNA replication in vertebrates.
  • The dynamic association of Y RNAs with chromatin throughout the cell cycle remains largely uncharacterized.

Purpose of the Study:

  • To quantify human Y RNA levels in different cellular fractions.
  • To investigate the dynamic topographical association of Y RNAs with chromatin during the cell cycle.
  • To explore the relationship between Y RNA and origin recognition complex (ORC) localization.

Main Methods:

  • Quantification of Y RNA levels in soluble and chromatin-associated fractions.
  • Cell cycle analysis to track Y RNA dynamics.
  • Comparison of Y RNA association in proliferating vs. quiescent cells and cancer vs. non-cancer cell lines.

Main Results:

  • Approximately one million Y RNA molecules are in the soluble fraction, with 5-10 fold less associated with chromatin in proliferating cells.
  • Y RNA levels significantly decrease during cellular quiescence.
  • Y RNAs associate with euchromatin throughout the cell cycle, with levels 2-4 fold higher in S phase compared to G1 or mitosis.
  • Y RNAs are absent at active DNA replication foci but re-associate with replicated euchromatin in mid to late S phase.
  • Y1 RNA chromatin association dynamics align with those of the origin recognition complex (ORC).

Conclusions:

  • Y RNA association with chromatin is cell cycle-dependent, peaking in S phase.
  • The observed dynamics suggest a functional interplay between Y RNAs and the origin recognition complex (ORC) in DNA replication.
  • Y RNAs may play a role in a common pathway with ORC during DNA replication initiation.