Structural Basis of LRPPRC-SLIRP-dependent Translation by the Mitoribosome

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2024 Aug 12

PMID 39134711

Authors

Vivek Singh

J Conor Moran

Yuzuru Itoh

Iliana C Soto

Flavia Fontanesi

Mary Couvillion

Martijn A Huynen

L Stirling Churchman

Antoni Barrientos

Alexey Amunts

Affiliations

Soon will be listed here.

Abstract

In mammalian mitochondria, mRNAs are cotranscriptionally stabilized by the protein factor LRPPRC (leucine-rich pentatricopeptide repeat-containing protein). Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-electron microscopy structure in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), 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 handoff of 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 RNA sequencing, metabolic labeling and mitoribosome profiling, which showed a transcript-specific influence on mRNA translation efficiency, with cytochrome c oxidase subunit 1 and 2 translation being the most affected. 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.

Citing Articles

Mettl15-Mettl17 modulates the transition from early to late pre-mitoribosome.

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LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.

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The human mitochondrial translation factor TACO1 alleviates mitoribosome stalling at polyproline stretches.

Brischigliaro M, Kruger A, Moran J, Antonicka H, Ahn A, Shoubridge E Nucleic Acids Res. 2024; 52(16):9710-9726.

PMID: 39036954 PMC: 11381339. DOI: 10.1093/nar/gkae645.

The human mitochondrial mRNA structurome reveals mechanisms of gene expression.

Moran J, Brivanlou A, Brischigliaro M, Fontanesi F, Rouskin S, Barrientos A Science. 2024; 385(6706):eadm9238.

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