Abstract
Cellular quiescence, a reversible state of cell cycle arrest, is characterized by profound alterations in gene expression and cellular function. While the role of histone modifications in regulating gene transcription during quiescence is well-established, their impact on post-transcriptional processes, particularly nuclear RNA export, remains less understood. This study investigates how specific histone modifications influence the efficiency and selectivity of nuclear RNA export in quiescent cells. We hypothesized that epigenetic marks associated with repressed chromatin states in quiescent cells would impede the export of certain RNA species, thereby contributing to the maintenance of the quiescent state. Employing a combination of molecular biology techniques, including chromatin immunoprecipitation sequencing (ChIP-seq) for key histone marks (H3K9me3, H3K27me3, H4K20me3) and quantitative RT-PCR to assess nuclear and cytoplasmic RNA levels, we analyzed the export profiles of various mRNA and non-coding RNA classes in quiescent versus proliferating human fibroblasts. Our results indicate a significant correlation between specific repressive histone marks, particularly H4K20me3, and reduced nuclear export of replication-dependent histone mRNAs and certain long non-coding RNAs. Conversely, actively transcribed genes in quiescent cells showed export patterns comparable to proliferating cells, suggesting a targeted rather than global disruption. We identified differential recruitment of nuclear export factors, such as TAP/NXF1, to specific RNA-protein complexes based on their association with modified chromatin. These findings highlight a critical, previously underappreciated layer of gene expression regulation during quiescence, where histone modifications directly impact RNA trafficking, influencing cellular fate decisions and response to stimuli. This work provides new insights into the complex interplay between epigenetics and RNA biology in maintaining cellular homeostasis.
Keywords
Histone modification, Nuclear RNA export, Cellular quiescence, Epigenetics, RNA trafficking, Gene expression regulation, H4K20me3, TAP/NXF1