Capping enzyme mRNA-cap/RNGTT regulates hedgehog pathway activity by antagonizing protein kinase A

Ping Chen, Zizhang Zhou, Xia Yao, Shu Pang, Meijing Liu, Weirong Jiang, Jin Jiang, Qing Zhang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Hedgehog (Hh) signaling plays a pivotal role in animal development and its deregulation in humans causes birth defects and several types of cancer. Protein Kinase A (PKA) modulates Hh signaling activity through phosphorylating the transcription factor Cubitus interruptus (Ci) and G protein coupled receptor (GPCR) family protein Smoothened (Smo) in Drosophila, but how PKA activity is regulated remains elusive. Here, we identify a novel regulator of the Hh pathway, the capping-enzyme mRNAcap, which positively regulates Hh signaling activity through modulating PKA activity. We provide genetic and biochemical evidence that mRNA-cap inhibits PKA kinase activity to promote Hh signaling. Interestingly, regulation of Hh signaling by mRNA-cap depends on its cytoplasmic capping-enzyme activity. In addition, we show that the mammalian homolog of mRNA-cap, RNGTT, can replace mRNA-cap to play the same function in the Drosophila Hh pathway and that knockdown of Rngtt in cultured mammalian cells compromised Shh pathway activity, suggesting that RNGTT is functionally conserved. Our study makes an unexpected link between the mRNA capping machinery and the Hh signaling pathway, unveils a new facet of Hh signaling regulation, and reveals a potential drug target for modulating Hh signaling activity.

Original languageEnglish (US)
Article number2891
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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mRNA guanylyltransferase
Hedgehogs
Cyclic AMP-Dependent Protein Kinases
Messenger RNA

ASJC Scopus subject areas

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Capping enzyme mRNA-cap/RNGTT regulates hedgehog pathway activity by antagonizing protein kinase A. / Chen, Ping; Zhou, Zizhang; Yao, Xia; Pang, Shu; Liu, Meijing; Jiang, Weirong; Jiang, Jin; Zhang, Qing.

In: Scientific Reports, Vol. 7, No. 1, 2891, 01.12.2017.

Research output: Contribution to journalArticle

Chen, Ping ; Zhou, Zizhang ; Yao, Xia ; Pang, Shu ; Liu, Meijing ; Jiang, Weirong ; Jiang, Jin ; Zhang, Qing. / Capping enzyme mRNA-cap/RNGTT regulates hedgehog pathway activity by antagonizing protein kinase A. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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AU - Jiang, Weirong

AU - Jiang, Jin

AU - Zhang, Qing

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