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bioRxiv · 10.1101/2022.06.20.496763

Activation mechanism of mitochondrial translation by LRPPRC-SLIRP

Singh, V.·Itoh, Y.·Huynen, M.·Amunts, A.
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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.

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Singh, V., Itoh, Y., Huynen, M., Amunts, A.. 2022-06-20. Activation mechanism of mitochondrial translation by LRPPRC-SLIRP. https://doi.org/10.1101/2022.06.20.496763

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