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| Item Type: | Article |
|---|---|
| Title: | Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart |
| Creators Name: | Milenkovic, I., Santos Vieira, H.G., Lucas, M.C., Ruiz-Orera, J., Patone, G., Kesteven, S., Wu, J., Feneley, M., Espadas, G., Sabidó, E., Hübner, N., van Heesch, S., Völkers, M. and Novoa, E.M. |
| Abstract: | The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally diverse 'specialized ribosomes' is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralogue of RPL3 (uL3) that is exclusively expressed in skeletal muscle and heart tissues, by generating a viable homozygous Rpl3l knockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes up-regulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L modulates neither translational efficiency nor ribosome affinity towards a specific subset of transcripts. In contrast, we show that depletion of RPL3L leads to increased ribosome-mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of fine-tuning of mitochondrial activity. Our results demonstrate that the existence of tissue-specific RP paralogues does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity. |
| Keywords: | Heart, Mammals, Mitochondria, Skeletal Muscle, Protein Biosynthesis, Ribosomal Proteins, Ribosomes, Animals, Mice |
| Source: | Nucleic Acids Research |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Volume: | 51 |
| Number: | 11 |
| Page Range: | 5301-5324 |
| Date: | 23 June 2023 |
| Official Publication: | https://doi.org/10.1093/nar/gkad121 |
| PubMed: | View item in PubMed |
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