Transcriptional profile of MESH1-silenced RCC4 cells

Nutrient deprivation triggers stringent response in bacteria, allowing rapid reallocation of resources from proliferation toward stress survival. Critical to this process is the accumulation of (p)ppGpp regulated by the RelA/SpoT homologues. While mammalian genomes encode MESH1—the homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Therefore, the function of MESH1 remains a mystery. Here, we report that genetic removal of MESH1 from human cell induce an extensive transcriptional response. The changes are distinct from the canonical unfolding protein response but strongly resemble the bacterial stringent response, which induce cell proliferation arrest, implicating MESH1 in a previously uncharacterized stress response in human cells. human clear cell renal carcinoma cell line RCC4 were transfected by two independent siRNA targeting MESH1 (siMESH1-CDS, siMESH1-3UTR=siMESH1-7002) and compared to the control with non-targeting siRNA (siNT). siMESH1-CDS: GGGAAUCACUGACAUUGUG, D-031786-01, Dharmacon siMESH1-3'UTR (siMESH1-7002): CTGAAGGTCTCCTGCTAACTA, SI04167002, Qiagen non-targeting siRNA (siNT, AllStars Negative Control siRNA, SI03650318).