| 2. |
- Singh, Vivek, et al.
(författare)
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Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)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 eight 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 onND1, ND2, ATP6, COX1, COX2,andCOX3mRNA translation efficiency. Taken together, our data suggest that LRPPRC-SLIRP does not preexist on the mitoribosome as its structural element but rather acts in recruitment of specific mRNAs to modulate their translation. Collectively, the data define LRPPRC-SLIRP as a regulator of the mitochondrial gene expression system.
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| 3. |
- Tobiasson, Victor, 1994-
(författare)
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On the Origin and Evolution of the Mitochondrial Ribosome
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ribosome is among the most ancient, intricate and well studied macromolecular complexes in biology. Predating the earliest divergence of life, its core molecular structure has remained mostly unchanged for more than three billion years. In stark contrast to its monolithic ancestor, the mitochondrial ribosome represents one of the most architecturally diverse protein complexes investigated. This work is an attempt at reconciling these two paradigms. In this thesis I first briefly cover the evolutionary history of the mitochondrial ribosome: from its ancient origins, through the process of Eukaryogenesis and the development of mitochondria, to its current state. Following this I present a comprehensive and integrated comparative analysis of the current mitoribosomal structures. Using these structural observations as a starting point I then summarise the current knowledge regarding the evolutionary trends of mitochondrial ribosomes. Finally I review and discuss potential genetic mechanisms and evolutionary pressures which could have produced such a vibrant diversity of structures. Together with this analysis I present monosome structures from the ciliate Tetrahymena thermophila and chlorophycean Polytomella magna together with an assembly intermediate of the large subunit from Trypanosoma brucei. Together, I hope to demonstrate the impact of the unique mitochondrial environment on the evolution of the mitochondrial ribosome.
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