TY - JOUR

T1 - Repeat RNAs associate with replication forks and post-replicative DNA

AU - Gylling, Helene M

AU - Gonzalez-Aguilera, Cristina

AU - Smith, Martin A

AU - Kaczorowski, Dominik C

AU - Groth, Anja

AU - Lund, Anders H

N1 - Published by Cold Spring Harbor Laboratory Press for the RNA Society.

PY - 2020

Y1 - 2020

N2 - Non-coding RNA has a proven ability to direct and regulate chromatin modifications by acting as scaffolds between DNA and histone-modifying complexes. However, it is unknown if ncRNA plays any role in DNA replication and epigenome maintenance, including histone eviction and re-instalment of histone-modifications after genome duplication. Isolation of nascent chromatin has identified a large number of RNA-binding proteins in addition to unknown components of the replication and epigenetic maintenance machinery. Here, we isolated and characterized long and short RNAs associated with nascent chromatin at active replication forks and track RNA composition during chromatin maturation across the cell cycle. Shortly after fork passage, GA-rich-, Alpha- and TElomeric Repeat-containing RNAs (TERRA) are associated with replicated DNA. These repeat containing RNAs arise from loci undergoing replication, suggesting an interaction in cis. Post-replication during chromatin maturation, and even after mitosis in G1, the repeats remain enriched on DNA. This suggests that specific types of repeat RNAs are transcribed shortly after DNA replication and stably associate with their loci of origin throughout cell cycle. The presented method and data enables studies of RNA interactions with replication forks and post-replicative chromatin and provides insights into how repeat RNAs and their engagement with chromatin are regulated with respect to DNA replication and across the cell cycle.

AB - Non-coding RNA has a proven ability to direct and regulate chromatin modifications by acting as scaffolds between DNA and histone-modifying complexes. However, it is unknown if ncRNA plays any role in DNA replication and epigenome maintenance, including histone eviction and re-instalment of histone-modifications after genome duplication. Isolation of nascent chromatin has identified a large number of RNA-binding proteins in addition to unknown components of the replication and epigenetic maintenance machinery. Here, we isolated and characterized long and short RNAs associated with nascent chromatin at active replication forks and track RNA composition during chromatin maturation across the cell cycle. Shortly after fork passage, GA-rich-, Alpha- and TElomeric Repeat-containing RNAs (TERRA) are associated with replicated DNA. These repeat containing RNAs arise from loci undergoing replication, suggesting an interaction in cis. Post-replication during chromatin maturation, and even after mitosis in G1, the repeats remain enriched on DNA. This suggests that specific types of repeat RNAs are transcribed shortly after DNA replication and stably associate with their loci of origin throughout cell cycle. The presented method and data enables studies of RNA interactions with replication forks and post-replicative chromatin and provides insights into how repeat RNAs and their engagement with chromatin are regulated with respect to DNA replication and across the cell cycle.

U2 - 10.1261/rna.074757.120

DO - 10.1261/rna.074757.120

M3 - Journal article

C2 - 32393525

VL - 26

SP - 1104

EP - 1117

JO - RNA

JF - RNA

SN - 1355-8382

IS - 9

ER -