Human lncRNA RMRP interacts with DEAD-box helicases and modulates mitochondrial function

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The human long noncoding RNA (lncRNA) RMRP is implicated in diseases but its structure and functions are unclear.
• RNase MRP complex component RMRP's role beyond this complex needs elucidation.

Purpose of the Study:

• To comprehensively analyze RMRP's structure, protein interactions, and mitochondrial roles.
• To understand the molecular mechanisms of RMRP in maintaining mitochondrial function.

Main Methods:

• Small-angle X-ray scattering (SAXS) to determine RMRP structure.
• Protein-RNA interaction studies with DEAD-box RNA helicases DDX5 and DDX3X.
• Analysis of mitochondrial function and gene expression upon RMRP level changes.

Main Results:

• RMRP exhibits Mg2+-dependent structural changes, adopting different conformations.
• DDX5 and DDX3X helicases interact with RMRP, influencing its localization and activity.
• Reduced RMRP levels impair mitochondrial stability, causing depolarization and increased ROS.
• RMRP regulates nuclear-encoded mitochondrial proteins DNAJC11 and NDUFS8.

Conclusions:

• RMRP is a structurally dynamic lncRNA crucial for mitochondrial integrity.
• RMRP collaborates with RNA helicases to maintain mitochondrial health via specific gene regulation.
• Findings offer insights into RMRP-related disorders and potential therapeutic strategies.