Ribosomal Protein S12e Has a Distinct Function in Cell Competition

Abstract

Wild-type Drosophila cells can remove cells heterozygous for ribosomal protein mutations (known as "Minute" mutant cells) from genetic mosaics, a process termed cell competition. The ribosomal protein S12 was unusual because cells heterozygous for rpS12 mutations were not competed by wild-type, and a viable missense mutation in rpS12 protected Minute cells from cell competition with wild-type cells. Furthermore, cells with Minute mutations were induced to compete with one another by altering the gene dose of rpS12, eliminating cells with more rpS12 than their neighbors. Thus RpS12 has a special function in cell competition that defines the competitiveness of cells. We propose that cell competition between wild-type and Minute cells is initiated by a signal of ribosomal protein haploinsufficiency mediated by RpS12. Since competition between cells expressing different levels of Myc did not require RpS12, other kinds of cell competition may be initiated differently.

Inter-Organ Growth Coordination Is Mediated by the Xrp1-Dilp8 Axis in Drosophila

“…Another potential candidate for this regulation is the atypical ribosomal protein RpS12, since it plays a role in Minute-induced cell competition (Kale et al, 2018). Consistent with its function as a ribosomal protein, silencing RpS12 in the wing pouch (pdm2>rpS12 RNAi ) leads to a strong autonomous inhibition of tissue growth ( Figure 4A).…”

Inter-organ growth coordination is mediated by the Xrp1/Dilp8 axis in Drosophila

“…Another potential candidate for this regulation is the ribosomal protein RpS12, since it plays a role in triggering minute-induced cell competition (Kale et al, 2018). Consistent with its function as a ribosomal protein, silencing RpS12 in the wing pouch (pdm2>rpS12 RNAi ) led to a strong autonomous inhibition of tissue growth ( Figure 4A).…”

Tumor evolution: Multiple induction mechanisms for cell competition

“…Drosophila genetics remains a valuable tool for discovering mechanisms of cell competition, and a new signal has now been found in the cell competition between Rp +/cells and wild type cells. Whenever a Rp gene is mutated, one particular ribosomal protein is important for initiating competition 10 . This special ribosomal protein, RpS12, is an essential protein like other ribosomal proteins but it has an additional role in determining competitiveness.…”

“…This is revealed when Rp +/cells that have more RpS12 get eliminated by Rp +/neighbors that have less RpS12 (where the Rp +/genotype affects any other ribosomal protein gene). Therefore, it seems that this cell competition depends on different relative levels of RpS12 activity 10 . The molecular mechanism of RpS12 signaling is not yet known.…”

“…The innate immune components involved in Rp +/and Myc induced competition are partially distinct4 . RpS12 is crucial in competitive elimination of Rp +/cells but is not required for Myc induced competition10 , meanwhile the Sas/PTP10D and Slit/Robo signals that eliminate preneoplastic cells are not important for eliminating Rp +/cells-1,2…”