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Title | Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 31, Issue 12, Page 1838-1847, Year 2024 |
Publish date | Aug 12, 2024 |
![]() | Vivek Singh / J Conor Moran / Yuzuru Itoh / Iliana C Soto / Flavia Fontanesi / Mary Couvillion / Martijn A Huynen / L Stirling Churchman / Antoni Barrientos / Alexey Amunts / ![]() ![]() ![]() ![]() ![]() |
PubMed 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 ...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. |
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Methods | EM (single particle) |
Resolution | 2.69 - 3.38 Å |
Structure data | EMDB-15544, PDB-8any: ![]() EMDB-16407: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (focussed on SSU head) ![]() EMDB-16408: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (focussed on SSU body) ![]() EMDB-16409: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (masked refined on SSU tail) ![]() EMDB-16410: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (focussed on LSU body) ![]() EMDB-16411: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (focussed on L10/L12 stalk) ![]() EMDB-16412: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (focussed on mS39-LRPPRC-SLIRP) ![]() EMDB-16413: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (focussed on central protuberance) ![]() EMDB-16414: Human mitochondrial ribosome in complex with LRPPRC-SLIRP, A-site, P-site, E-site tRNAs and mRNA (consensus) |
Chemicals | ![]() ChemComp-NAD: ![]() ChemComp-SPM: ![]() ChemComp-SPD: ![]() ChemComp-MG: ![]() ChemComp-K: ![]() ChemComp-ZN: ![]() ChemComp-FES: ![]() ChemComp-ATP: ![]() ChemComp-GDP: ![]() ChemComp-PUT: ![]() ChemComp-VAL: ![]() ChemComp-HOH: |
Source |
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![]() | RIBOSOME / mitochondrial translation / mRNA delivery |