The RNA exosome contributes to gene expression regulation during stem cell differentiation

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Gene expression changes are crucial for cellular transitions like embryonic stem cell (ESC) differentiation.
• Transcription factors and chromatin modifiers are known regulators of RNA levels.
• The role of nuclear RNA decay in differentiation remains largely unexplored.

Purpose of the Study:

• To investigate the contribution of nuclear RNA decay, specifically by the RNA exosome, to gene expression changes during mouse ESC differentiation.
• To determine the extent to which RNA abundance differences between states are due to transcription versus RNA decay.

Main Methods:

• Differentiation of mouse ESCs into embryoid bodies.
• Depletion of the ribonucleolytic RNA exosome and its cofactor RBM7.
• Analysis of RNA abundance and stability in depleted versus control cells.

Main Results:

• Exosome depletion primarily stabilizes RNAs from lowly transcribed loci, including protein-coding genes.
• Depletion of the nuclear exosome cofactor RBM7 produced similar RNA stabilization effects.
• Transcripts with differential expression between cell states were more sensitive to exosome activity when their expression was low.

Conclusions:

• The nuclear RNA exosome plays a significant role in down-regulating specific transcripts during cellular differentiation.
• RNA exosome activity often works in concert with transcriptional down-regulation to control gene expression.
• Nuclear RNA decay is an important post-transcriptional process influencing cell fate decisions.