Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Centromeres were historically considered transcriptionally silent.
• Emerging evidence indicates active transcription from centromeric regions.
• The functional role and regulation of centromere-derived RNAs remain poorly understood.

Purpose of the Study:

• To investigate the behavior and regulation of alpha-satellite RNA transcripts originating from human centromeres.
• To elucidate the mechanisms controlling centromere transcription and its potential impact on chromatin dynamics.

Main Methods:

• Utilized single-molecule fluorescence in-situ hybridization (smFISH) to visualize alpha-satellite RNA in intact human cells.
• Assessed the dependence of alpha-satellite transcription on RNA polymerase II, centromere components, and cell division machinery.
• Examined the correlation between centromere-nucleolar interactions and alpha-satellite RNA levels.

Main Results:

• Alpha-satellite RNA transcripts were detected and their levels varied across cell lines and the cell cycle.
• Transcripts were not consistently localized to centromeres, behaving like other long non-coding RNAs.
• Transcription is RNA polymerase II-dependent but independent of canonical centromere/cell division factors.
• Centromere-nucleolar interactions were found to repress alpha-satellite expression.
• Disruption of the nucleolus led to a substantial increase in alpha-satellite transcript levels.

Conclusions:

• Centromere transcription is actively regulated, with nucleolar interactions playing a key repressive role.
• Centromere-nucleolar contacts provide a novel mechanism for modulating centromere transcription and chromatin dynamics.
• This regulation offers insights into cellular adaptability across different states and conditions.