Related Experiment Video
Updated: Jun 23, 2025
08:53
Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
Published on: May 2, 2025
319
ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins
Mathew Thayer1, Michael B Heskett2,3, Leslie G Smith1
1Department of Chemical Physiology and Biochemistry,Oregon Health & Science University, Portland, United States.
Elife
|June 19, 2024
Summary
Very-long noncoding RNAs called ASARs are crucial for chromosome stability and replication timing. They act as scaffolds, assembling hnRNP complexes to maintain mammalian chromosome structure.
Area of Science:
- Genetics
- Molecular Biology
- Epigenetics
Background:
- Very-long noncoding RNAs (ASARs) are essential for controlling replication timing on human autosomes and maintaining chromosome stability.
- ASARs are known to associate with their parent chromosomes.
Purpose of the Study:
- To investigate the role of ASARs in genome-wide replication timing.
- To identify RNA-binding proteins (RBPs) that interact with ASARs.
- To elucidate the mechanism by which ASARs regulate replication timing and chromosome structure.
Main Methods:
- Analysis of RNA-protein interaction data (ENCODE).
- Genetic deletion and ectopic integration assays.
- shRNA-mediated depletion of RBPs.
- Assessing ASAR lncRNA localization and replication timing.
Main Results:
- Numerous RBPs, particularly hnRNPs, interact with ASAR lncRNAs.
- A specific domain within ASAR6-141 is rich in RBP interaction sites and controls replication timing in cis.
- Depletion of specific hnRNPs causes ASARs to detach from chromosomes and disrupts synchronous replication, mimicking ASAR knockout effects.
- ASARs play a role in the temporal order of genome-wide replication.
Conclusions:
- ASARs function as critical RNA scaffolds for assembling hnRNP complexes.
- These complexes are vital for maintaining the structural integrity of mammalian chromosomes.
- ASARs are key regulators of replication timing and chromosome stability.
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