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Free keywords:
Animals
Binding Sites
Fibroblasts
Genome, Mitochondrial/physiology
Humans
Male
Mice, Inbred C57BL
Mice, Knockout
Mitochondria/*physiology
Molecular Chaperones/physiology
Neoplasm Proteins/*physiology
Polyadenylation/physiology
Protein Binding/physiology
Protein Biosynthesis/physiology
Protein Footprinting/methods
RNA Folding/*physiology
RNA Stability/physiology
RNA, Messenger/genetics/metabolism
RNA-Binding Proteins/*physiology
Recombinant Proteins/genetics/metabolism
Sequence Analysis, RNA/methods
Transcriptome/*physiology
Abstract:
The expression of the compact mammalian mitochondrial genome requires transcription, RNA processing, translation and RNA decay, much like the more complex chromosomal systems, and here we use it as a model system to understand the fundamental aspects of gene expression. Here we combine RNase footprinting with PAR-CLIP at unprecedented depth to reveal the importance of RNA-protein interactions in dictating RNA folding within the mitochondrial transcriptome. We show that LRPPRC, in complex with its protein partner SLIRP, binds throughout the mitochondrial transcriptome, with a preference for mRNAs, and its loss affects the entire secondary structure and stability of the transcriptome. We demonstrate that the LRPPRC-SLIRP complex is a global RNA chaperone that stabilizes RNA structures to expose the required sites for translation, stabilization, and polyadenylation. Our findings reveal a general mechanism where extensive RNA-protein interactions ensure that RNA is accessible for its biological functions.
