Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization

Area of Science:

• Mitochondrial biology
• Molecular genetics
• RNA biology

Background:

• The mitochondrial genome's 13 oxidative phosphorylation components are crucial for cellular energy production.
• Dysregulated mitochondrial transcription is linked to numerous human diseases.
• 7S RNA, a non-coding RNA, is rapidly modulated by physiological changes.

Purpose of the Study:

• To investigate the regulatory role of 7S RNA in mitochondrial transcription.
• To elucidate the mechanism by which 7S RNA controls mitochondrial gene expression.

Main Methods:

• In vitro transcription assays.
• Cultured human cell experiments.
• Cryo-electron microscopy (cryo-EM) to determine structural interactions.

Main Results:

• 7S RNA was found to regulate mitochondrial transcription levels both in vitro and in cultured cells.
• Cryo-EM revealed that 7S RNA induces the dimerization of RNA polymerase (POLRMT).
• The POLRMT dimer interface, formed upon 7S RNA binding, blocks promoter recognition and unwinding, inhibiting transcription.

Conclusions:

• 7S RNA acts as a negative regulator of mitochondrial transcription in mammalian cells.
• The 7S RNA-POLRMT interaction forms a critical component of a negative feedback loop for mitochondrial gene expression control.