Motif-driven interactions between RNA and PRC2 are rheostats that regulate transcription elongation

Area of Science:

• Molecular Biology
• Epigenetics
• Gene Regulation

Background:

• Polycomb repressive complex 2 (PRC2) is an RNA-binding complex.
• The specific RNA binding motifs and the role of PRC2-RNA complexes at active genes are not fully understood.

Purpose of the Study:

• Identify high-affinity RNA motifs that bind PRC2.
• Elucidate the function of PRC2-RNA complexes in regulating gene transcription and repression.

Main Methods:

• Mutation analysis of RNA motifs to assess PRC2 binding.
• Analysis of PRC2-RNA complex association with active genes and RNA polymerase II (POL-II) pausing.
• Investigating the impact of PRC2 ablation on gene expression and transcription elongation.

Main Results:

• Identified specific RNA motifs that bind PRC2, with mutations weakening binding and repressive function.
• PRC2-RNA interactions occur at promoter-proximal regions, often coinciding with POL-II pausing.
• Ablating PRC2 increases gene expression by reducing pausing and enhancing elongation.
• Nascent RNA targets PRC2 in cis to downregulate neighboring genes.

Conclusions:

• PRC2-nascent RNA complexes act as transcriptional rheostats, fine-tuning gene expression by modulating pausing and elongation.
• This mechanism explains the frequent association of PRC2-RNA complexes with active genes.
• RNA recruits PRC2 to repress genes via POL-II pausing and histone H3 trimethylation (Lys27).