Metazoan stringent-like response mediated by MESH1 phenotypic conservation via distinct mechanisms

From magic spot ppGpp to MESH1: Stringent response from bacteria to metazoa

“…Another study of MESH1 in Caenorhabditis elegans also reported the induction of unfolding protein response upon MESH1 removal [ 31 ]. Therefore, there are significant similarities between the bacterial and metazoan stringent response across evolution, prompting us to coin the term of “metazoan stringent-like response” [ 32 ].…”

“…Similarly, MESH1 knockdown in cancer cells also triggers similar sets of biological processes as well as the phenotypic features of stress survival, proliferation arrests, and transcriptional reprogramming that are highly similar to bacterial stringent response ( Fig 1 ). Therefore, we termed these phenotypic responses to MESH1 inhibition as metazoan stringent-like response [ 32 ]. However, while (p)ppGpp binds and modulates various molecular targets in bacteria, several additional pathways (such as TAZ, integrative stress response) connect MESH1 to downstream biological processes ( Fig 1 ).…”

Data on the transcriptional response to MESH1 knockdown and mammalian stringent response

“…To define the transcriptional response to MESH1 knockdown, we knockdown MESH1 in H1975 cells with independent siRNAs and performed transcriptomic analysis [2] .…”

Protein–Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions

“…The response was dubbed a ‘stringent-like response’ by the authors; however, this response turned out to be fundamentally different from the canonical stringent response in prokaryotes. Also noteworthy is that MESH1 appears to be an ortholog of SpoT in sequence and structure ( Figure 7 ), but not in function, and that it has no synthetase activity [ 134 ]. In complementary reports, ppGpp was identified as an alarmone in the fruit fly, in human cells [ 13 ], and in a few plant chloroplasts [ 14 , 15 ].…”