Abstract
In mammalian mitochondria, mRNAs are co-transcriptionally stabilized by the protein factor LRPPRC. Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-EM structure in complex with SLIRP, mRNA and the mitoribosome. The structure shows that LRPPRC associates with the mitoribosomal proteins mS39 and the N-terminus of mS31 through recognition of the LRPPRC helical repeats. Together, the proteins form a corridor for hand-off the mRNA. The mRNA is directly bound to SLIRP, which also has a stabilizing function for LRPPRC. To delineate the effect of LRPPRC on individual mitochondrial transcripts, we used an RNAseq approach, metabolic labeling and mitoribosome profiling that showed a major influence on ND1, ND2, ATP6, COX1, COX2, and COX3 mRNA translation efficiency. Our data suggest that LRPPRC-SLIRP acts in recruitment of mitochondrial mRNAs to modulate their translation. Collectively, the data define LRPPRC-SLIRP as a regulator of the mitochondrial gene expression system.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We thank Reviewers #1 and #2 for taking the time to go through the manuscript again and approving it. We thank Reviewer #3 for providing additional constructive suggestions on how to improve the study and its presentation. In the revised version, we addressed all the requests and followed the valuable suggestions.
