Putrescine independent wound response phenotype is produced by ODC-like RNAi in planarians

Despite increasing evidence indicates polyamines as a convergence point for signaling pathways driving cellular functions, including cell growth and differentiation, a unifying concept to interpret their role is still missing. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is tightly regulated by a complex molecular machinery, and the recent demonstration of the existence of multiple ODC paralogs, lacking decarboxylation activity, suggests additional layers of complexity to the already intricate ODC regulatory pathway. Because of their extraordinary regenerative abilities and great abundance of adult stem cell, planarians have a great potential to contribute to our understanding of polyamine function in an in vivo context. For this reason, we undertook a study on ODC function in planarians and we found six planarian ODCs (ODC1-6). ). Five out of six ODC homologs carry substitutions of key aminoacids involved in enzymatic activity, which makes them theoretically unable to decarboxylate ornithine. Silencing of ODC5 and 6 produced a complex phenotype, by prompting animals to an aberrant response, following chronic injury without tissue removal. RNAi phenotype is neither rescued by putrescine, nor mimicked by Difluoromethylornithine treatment. Moreover, the co-silencing of other genes of the ODC regulatory pathway did not modulate phenotype outcome or severity, thus suggesting that the function/s of these ODC-like proteins might be unrelated to decarboxylase activity and putrescine production.