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Publication : RNA homeostasis governed by cell type-specific and branched feedback loops acting on NMD.

First Author  Huang L Year  2011
Journal  Mol Cell Volume  43
Issue  6 Pages  950-61
PubMed ID  21925383 Mgi Jnum  J:251767
Mgi Id  MGI:6100753 Doi  10.1016/j.molcel.2011.06.031
Citation  Huang L, et al. (2011) RNA homeostasis governed by cell type-specific and branched feedback loops acting on NMD. Mol Cell 43(6):950-61
abstractText  Nonsense-mediated mRNA decay (NMD) is a conserved RNA decay pathway that degrades aberrant mRNAs and directly regulates many normal mRNAs. This dual role for NMD raises the possibility that its magnitude is buffered to prevent the potentially catastrophic alterations in gene expression that would otherwise occur if NMD were perturbed by environmental or genetic insults. In support of this, here we report the existence of a negative feedback regulatory network that directly acts on seven NMD factors. Feedback regulation is conferred by different branches of the NMD pathway in a cell type-specific and developmentally regulated manner. We identify feedback-regulated NMD factors that are rate limiting for NMD and demonstrate that reversal of feedback regulation in response to NMD perturbation is crucial for maintaining NMD. Together, our results suggest the existence of an intricate feedback network that maintains both RNA surveillance and the homeostasis of normal gene expression in mammalian cells.
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