During translation, a number of obstacles have the potential to arrest the ribosomal movement. In yeast, several studies revealed that the evolutionarily conserved Pelota (Pelo) recognizes stalled ribosomes and dissociates ribosomal subunits. In mammals, little is known about the role of Pelo in the ribosome-rescue machinery. An international collaboration with the participation of Prof. Ibrahim Adham at the Institute of Human Genetics Göttingen has studied conditional mouse lines in which Pelo is deleted in different epidermal stem cell lineages. They found that loss of the ribosome-rescue factor Pelo in specific epidermal stem cell lineage results in hyperproliferation and altered differentiation of these cells. By contrast, deletion of Pelo in other epidermal stem cell lineages has no effect or induces a mild phenotype. Further molecular analyses demonstrated that the Pelo deletion results in global upregulation of translation, rather than affecting the expression of specific genes. These results reveal that the ribosome-rescue machinery is essential for mammalian tissue homeostasis.
The results of the study have been published in Nature.
Liakath-Ali K, Mills EW, Sequeira I, Lichtenberger BM, Pisco AO, Sipilä KH, Mishra A, Yoshikawa H, Wu CC, Ly T, Lamond AI, Adham IM, Green R, Watt FM. An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis. Nature. 2018 Apr;556(7701):376-380. doi: 10.1038/s41586-018-0032-3. Epub 2018 Apr 11.