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

Abstract

Calcium ion (Ca2+) is a ubiquitous intracellular and extracellular messenger that regulates several cellular activities. Previous findings have reported the presence of active Ca2+ receptors in mouse embryonic stem cells (mESCs) but the fundamental requirement of Ca2+ signalling remains unclear. We have noted the presence of high Ca2+ 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 Ca2+ regulates the homeostasis and stability of Oct4 and Nanog at the post-translational level through pCamkII dependent mechanism independent of polyubiquitin system, JAK-STAT3 pathway, transcriptional and translational control. Our data also signifies the role of Ca2+ at the post-transcriptional level in regulating p-bodies and stress granule markers (Dcp1a, XRN1, Tudor and EDC4), splicing-dependent and 3UTR-dependent NMD activity. Together, this study identifies the broad role of Ca2+ in modulating key processes in mESCs. HighlightsCa2+ is present at elevated levels in mESCs and is important for pluripotency Ca2+ depletion accelerates G2/M cell cycle arrest and mesoderm differentiation Ca2+ regulates pluripotency and p-bodies markers at the post-translational level Ca2+ regulates Oct4, Nanog, dcp1a through pCaMKII dependent mechanism