RNA structure maps across mammalian cellular compartments

Area of Science:

• Molecular Biology
• Genomics
• Epigenetics

Background:

• RNA secondary structure is crucial for gene expression regulation.
• Previous methods lacked resolution to map RNA structures across cellular compartments.
• Understanding RNA structuromes in distinct subcellular locations is vital for deciphering gene regulation.

Purpose of the Study:

• To map and analyze RNA secondary structures (structuromes) within human and mouse cell compartments: chromatin, nucleoplasm, and cytoplasm.
• To investigate the role of RNA structure in connecting transcription, translation, and RNA decay.
• To develop a resource for visualizing RNA-protein interactions, RNA modifications, and their impact on RNA structure and function.

Main Methods:

• Development of high-resolution techniques to map RNA structuromes across subcellular compartments.
• Bioinformatic analysis to integrate RNA structure data with RNA-protein interactions and modifications.
• Experimental validation of predicted RNA-protein interactions and roles in RNA modification reading.

Main Results:

• Comprehensive maps of RNA structuromes in chromatin, nucleoplasm, and cytoplasm were generated.
• Detailed insights into how RNA structure links transcription, translation, and RNA decay were obtained.
• A novel function of the RNA-binding protein LIN28A as an N6-methyladenosine modification 'anti-reader' was validated.

Conclusions:

• RNA structuromes are dynamic and vary across subcellular compartments, significantly influencing gene regulation.
• The developed resource facilitates the study of RNA structure, modification, and protein interactions.
• LIN28A's role as an 'anti-reader' highlights novel mechanisms in RNA modification-based gene regulation.