Calcium: Modulator of Post-transcriptional and post-translational process in mESCs

Calcium ion (Ca ²⁺ ) is a ubiquitous intracellular and extracellular messenger that regulates several cellular activities. Previous findings have reported the presence of active Ca ²⁺ receptors in mouse embryonic stem cells (mESCs) but the fundamental requirement of Ca ²⁺ signalling remains unclear. We have noted the presence of high Ca ²⁺ in undifferentiated mESCs and showed that its depletion exerts G2/M cell cycle arrest, spontaneous differentiation of mESCs towards mesoderm lineage and mitochondrial biogenesis. Further, our data demonstrates that Ca ²⁺ regulates the homeostasis and stability of Oct4 and Nanog at the post-translational level through pCamkIIα dependent mechanism independent of polyubiquitin system, JAK-STAT3 pathway, transcriptional and translational control. Our data also signifies the role of Ca ²⁺ at the post-transcriptional level in regulating p-bodies and stress granule markers (Dcp1a, XRN1, Tudor and EDC4), splicing-dependent and 3’UTR-dependent NMD activity. Together, this study identifies the broad role of Ca ²⁺ in modulating key processes in mESCs.