Quantitative mapping of RNA-mediated nuclear estrogen receptor β interactome in human breast cancer cells

Area of Science:

• Molecular Biology
• Cancer Research
• Proteomics

Background:

• The estrogen receptor 2 (ESR2, ERβ) is a nuclear receptor with a known oncosuppressive role in breast cancer (BC).
• Previous studies indicated that RNA is involved in the assembly and function of the ERβ interactome.
• Understanding ERβ's protein interactions is crucial for deciphering its role in BC progression.

Purpose of the Study:

• To identify novel nuclear ERβ interactors in breast cancer cells.
• To investigate the role of RNA in mediating ERβ protein complex formation.
• To provide a comprehensive dataset of ERβ-associated proteins for further research in BC.

Main Methods:

• Native protein complex purification followed by nano liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Analysis of protein-RNA interactions by comparing results before and after in vitro RNA removal.
• Interaction proteomics using tandem affinity purification coupled to mass spectrometry.

Main Results:

• A large dataset of newly identified nuclear ERβ interactors was generated.
• A subset of ERβ interactors was found to associate with the receptor via RNA bridging.
• The study confirmed the involvement of RNA in ERβ interactome assembly and function.

Conclusions:

• This research expands the understanding of ERβ's molecular interactions in breast cancer.
• The identified ERβ interactors and the role of RNA provide new avenues for BC research.
• The generated datasets can facilitate further investigations into ERβ, nuclear RNAs, and their associated proteins in BC and other cell types.