1. Phospholipase Cβ connects G protein signaling with RNA interference.
- Author
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Scarlata S, Garwain O, Williams L, Burguera IG, Rosati B, Sahu S, Guo Y, Philip F, and Golebiewska U
- Subjects
- Animals, Binding Sites, Binding, Competitive, Calcium metabolism, Cell Membrane metabolism, Cytosol metabolism, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, HEK293 Cells, Humans, Phospholipase C beta metabolism, Protein Binding, RNA, Small Interfering metabolism, RNA-Induced Silencing Complex metabolism, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, Phospholipase C beta genetics, RNA Interference, RNA, Small Interfering genetics, RNA-Induced Silencing Complex genetics, Signal Transduction genetics
- Abstract
Phosphoinositide-specific-phospholipase Cβ (PLCβ) is the main effector of Gαq stimulation which is coupled to receptors that bind acetylcholine, bradykinin, dopamine, angiotensin II as well as other hormones and neurotransmitters. Using a yeast two-hybrid and other approaches, we have recently found that the same region of PLCβ that binds Gαq also interacts with Component 3 Promoter of RNA induced silencing complex (C3PO), which is required for efficient activity of the RNA-induced silencing complex. In purified form, C3PO competes with Gαq for PLCβ binding and at high concentrations can quench PLCβ activation. Additionally, we have found that the binding of PLCβ to C3PO inhibits its nuclease activity leading to reversal of RNA-induced silencing of specific genes. In cells, we found that PLCβ distributes between the plasma membrane where it localizes with Gαq, and in the cytosol where it localizes with C3PO. When cells are actively processing small interfering RNAs the interaction between PLCβ and C3PO gets stronger and leads to changes in the cellular distribution of PLCβ. The magnitude of attenuation is specific for different silencing RNAs. Our studies imply a direct link between calcium responses mediated through Gαq and post-transcriptional gene regulation through PLCβ., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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