MECP2 binds DGCR8

Stable Identifier
R-HSA-9022315
Type
Reaction [binding]
Species
Homo sapiens
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Based on studies in mice, MECP2, phosphorylated at serine residue S80, binds to DGCR8. The interaction involves the C-terminus of MECP2 and the RNA binding domain-containing C-terminus of DGCR8. Binding to MECP2 may interfere with the interaction between DGCR8 and DROSHA, as well as DGCR8 and primary microRNAs. As DGCR8 and DROSHA form the microprocessor complex which cleaves primary microRNAs (pri-miRNAs) into pre-miRNAs, binding of MECP2 to DGCR8 results in decreased pri-miRNA processing. One of the miRNAs affected by the interaction between MECP2 and DGCR8 is miR-134. miR-134 is highly expressed in brain where it inhibits translation of CREB1, LIMK1 and Pumilio2 mRNAs (Cheng et al. 2014). In addition to DGCR8, MECP2 was reported to bind to other components of the DROSHA microprocessor complex, including DROSHA. Instead of preventing formation of the microprocessor complex, MECP2 was reported to modulate its activity, targeting the complex to specific microRNAs. One of the microRNAs whose processing into a mature product is enhanced in the presence of MECP2 is miR-199a. Expression of several proteins that inhibit mTOR signaling is negatively regulated by miR-199a, creating a mechanistic link between MECP2 loss-of-function and decreased mTOR signaling in Rett syndrome (Tsujimura et al. 2015).

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