Ribosomes are responsible for protein synthesis in all living organisms and can exhibit specialised functions as a result of naturally occurring heterogeneous structures, according to recent studies. In this paper, the authors investigate a specific ribosomal protein, RPL3L, which is expressed exclusively in skeletal muscle and heart tissues, by developing a viable homozygous Rpl3l knockout mouse strain. They report that when the Rpl3l gene is deleted in mouse models, the missing RPL3L protein is replaced by its paralogue, RPL3, through a rescue mechanism. Specifically, RPL3 upregulation yields RPL3-containing ribosomes rather than RPL3L-containing ribosomes which are usually found in cardiomyocytes.

Both ribosome profiling and Nano-TRAP (a novel orthogonal approach involving ribosome pulldown and nanopore sequencing) were also employed, and they found that RPL3L does not affect translational efficiency or ribosome affinity to specific subsets of transcripts. The authors also found that ribosomes containing RPL3 establish closer interactions with mitochondria. This resulted in higher energy production compared to ribosomes containing RPL3L. Furthermore, they also observed this RPL3-RPL3L rescue mechanism in certain heart disease conditions like myocardial infarction and hypertrophy. In summary, the study demonstrates that ribosome heterogeneity can alter ribosome localisation without altering how ribosomes translate mRNA.