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miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus.

Publication ,  Journal Article
Han, Q; Liu, D; Convertino, M; Wang, Z; Jiang, C; Kim, YH; Luo, X; Zhang, X; Nackley, A; Dokholyan, NV; Ji, R-R
Published in: Neuron
August 8, 2018

Increasing evidence suggests that extracellular miRNAs may serve as biomarkers of diseases, but the physiological relevance of extracellular miRNA is unclear. We find that intradermal cheek injection of miR-711 induces TRPA1-depedent itch (scratching) without pain (wiping) in naive mice. Extracellular perfusion of miR-711 induces TRPA1 currents in both Trpa1-expressing heterologous cells and native sensory neurons through the core sequence GGGACCC. Computer simulations reveal that the core sequence binds several residues at the extracellular S5-S6 loop of TRPA1, which are critical for TRPA1 activation by miR-711 but not allyl isothiocyanate. Intradermal inoculation of human Myla cells induces lymphoma and chronic itch in immune-deficient mice, associated with increased serum levels of miR-711, secreted from cancer cells. Lymphoma-induced chronic itch is suppressed by miR-711 inhibitor and a blocking peptide that disrupts the miR-711/TRPA1 interaction. Our findings demonstrated an unconventional physiological role of extracellular naked miRNAs as itch mediators and ion channel modulators.

Duke Scholars

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Published In

Neuron

DOI

EISSN

1097-4199

Publication Date

August 8, 2018

Volume

99

Issue

3

Start / End Page

449 / 463.e6

Location

United States

Related Subject Headings

  • TRPA1 Cation Channel
  • Pruritus
  • Protein Binding
  • Neurology & Neurosurgery
  • Middle Aged
  • MicroRNAs
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
 

Citation

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Han, Q., Liu, D., Convertino, M., Wang, Z., Jiang, C., Kim, Y. H., … Ji, R.-R. (2018). miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. Neuron, 99(3), 449-463.e6. https://doi.org/10.1016/j.neuron.2018.06.039
Han, Qingjian, Di Liu, Marino Convertino, Zilong Wang, Changyu Jiang, Yong Ho Kim, Xin Luo, et al. “miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus.Neuron 99, no. 3 (August 8, 2018): 449-463.e6. https://doi.org/10.1016/j.neuron.2018.06.039.
Han Q, Liu D, Convertino M, Wang Z, Jiang C, Kim YH, et al. miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. Neuron. 2018 Aug 8;99(3):449-463.e6.
Han, Qingjian, et al. “miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus.Neuron, vol. 99, no. 3, Aug. 2018, pp. 449-463.e6. Pubmed, doi:10.1016/j.neuron.2018.06.039.
Han Q, Liu D, Convertino M, Wang Z, Jiang C, Kim YH, Luo X, Zhang X, Nackley A, Dokholyan NV, Ji R-R. miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. Neuron. 2018 Aug 8;99(3):449-463.e6.
Journal cover image

Published In

Neuron

DOI

EISSN

1097-4199

Publication Date

August 8, 2018

Volume

99

Issue

3

Start / End Page

449 / 463.e6

Location

United States

Related Subject Headings

  • TRPA1 Cation Channel
  • Pruritus
  • Protein Binding
  • Neurology & Neurosurgery
  • Middle Aged
  • MicroRNAs
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred C57BL