An international team of researchers led by the Max Delbruck Center Berlin (Germany) reports novel proteins made by the ribosomes in cardiomyocytes of healthy people and patients with dilated cardiomyopathy (DCM). While transcriptional processes are relatively well understood, there are still many questions about the translation of mRNA into protein in the ribosomes. Using ribosome profiling (ribo-seq), the team determined for the first time in human heart tissue, which proteins are formed during translation. They discovered a whole series of tiny, previously unknown ‘microproteins’ encoded by RNAs thought to be non-coding so far. Many of them were evolutionarily young substances that could not be detected, eg in mouse hearts. Most mini-proteins appeared to be used for energy production in the mitochondria.
In order to detect possible differences in the translatome between diseased and healthy hearts, the team examined tissue samples of 65 patients with DCM and 15 non-failing heart tissues. The DCM samples included many with a truncating mutation in TTN, the main cardiomyopathy gene coding for the sarcomere protein titin (1, 2). Interestingly, they observed that sometimes the ribosomes can ignore the stop signal due to the TTN truncation, such that near-wildtype proteins are being made. These findings may change our view on how gene truncations cause cardiomyopathy and may raise new possibilities for the treatment of these patients.