ASAR RNAs Control Replication Timing Through RNA-Protein Interactions

Khái niệm cốt lõi

The author argues that ASAR RNAs control replication timing through interactions with RNA binding proteins, demonstrating their essential role in maintaining chromosome stability.

Tóm tắt

The study focuses on ASAR RNAs' role in controlling replication timing and chromosome stability. It identifies key RBPs interacting with ASAR RNAs and demonstrates the impact of their depletion on replication timing across all autosome pairs. The findings suggest a crucial function for ASARs as essential RNA scaffolds for maintaining chromosomal integrity.

The research highlights the significance of an ∼7kb domain within ASAR6-141 RNA, showing its critical role in controlling replication timing of entire chromosomes. Depletion of specific RBPs results in dissociation of ASAR RNAs from chromosome territories, disrupting synchronous replication on all autosome pairs. These results emphasize the intricate relationship between ASAR RNAs and RBPs in regulating genome-wide replication dynamics.

Furthermore, the study explores the potential mechanisms by which ASARs interact with RBPs to influence replication timing, proposing a model where ASAR RNAs serve as scaffolds for forming protein complexes that regulate chromatin structure and DNA replication machinery. The findings suggest a novel perspective on how non-coding RNAs contribute to genome-wide processes such as chromosome dynamics and replication timing.

Thống kê

An ∼7kb domain within the ASAR6-141 RNA shows significant RBP interaction sites.
Genetic deletion of this ∼7kb domain results in delayed replication timing.
Depletion of HNRNPA1, HNRNPC, HNRNPL, HNRNPM, HNRNPU, or HNRNPUL1 disrupts synchronous replication on autosome pairs.

Trích dẫn

"The ∼7kb RBP domain represents a critical region within the ASAR6-141 gene that controls replication timing."
"Depletion of specific RBPs results in loss of chromosome territory association of multiple ASAR RNAs."
"ASARs play an essential role during the temporal order of genome-wide replication."

Thông tin chi tiết chính được chắt lọc từ

ASAR lncRNAs control DNA replication timing through interactions with multiple hnRNP/RNA binding proteins

by Thayer,M. J.... lúc www.biorxiv.org 06-04-2022

https://www.biorxiv.org/content/10.1101/2022.06.04.494840v3

Yêu cầu sâu hơn

How do other non-coding RNAs compare to ASARs in terms of regulating genome-wide processes

Other non-coding RNAs, such as C0T-1 RNA, repRNA, caRNA, and "RNA debris," have been implicated in various chromosome dynamics within the nucleus. However, ASARs stand out due to their genetic validation and functional role in controlling replication timing of individual human autosomes. While other non-coding RNAs may play roles in chromatin organization or nuclear structure maintenance, ASARs have been shown to be essential for maintaining synchronous replication between pairs of autosomes. The unique characteristics of ASARs, including their epigenetically regulated allelic expression imbalance (AEI) and variable epigenetic replication timing (VERT), set them apart from other non-coding RNAs.

What are potential implications of disrupting synchronous replication on autosome pairs

Disrupting synchronous replication on autosome pairs can have significant implications for genome stability and function. When replication is not synchronized between homologous chromosomes, it can lead to genomic instability, DNA damage accumulation, and potential errors during cell division. This asynchrony could result in unequal distribution of genetic material between daughter cells during mitosis or meiosis. Additionally, disruptions in replication timing may impact gene expression patterns and regulatory mechanisms that rely on precise temporal coordination during the cell cycle.

How might understanding the interaction between ASARs and RBPs contribute to advancements in genetic research

Understanding the interaction between ASARs and RBPs holds promise for advancements in genetic research by shedding light on the molecular mechanisms underlying chromosome dynamics and genome-wide processes like replication timing control. By elucidating how ASARs serve as scaffolds for assembling RNA-protein complexes involving multiple hnRNPs/RBPs that regulate chromosome territories' structural integrity and synchronization of DNA replication across autosomes, researchers can gain insights into fundamental aspects of nuclear organization. This knowledge could pave the way for developing targeted therapies or interventions aimed at modulating these interactions to correct aberrant genome-wide processes associated with diseases or disorders related to chromosomal instability or altered gene regulation.