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

Qingjian Han, Di Liu, Marino Convertino, Zilong Wang, Changyu Jiang, Yong Ho Kim, Xin Luo, Xin Zhang, Andrea Nackley, Nikolay V. Dokholyan, Ru Rong Ji

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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. How extracellular miRNA signals is unclear. Han et al. describe that miRNA-711, secreted from inoculated lymphoma cells on the back skin, binds TRPA1 ion channels extracellularly on pruriceptive neurons to drive acute and chronic itch via specific core sequence.

Original languageEnglish (US)
Pages (from-to)449-463.e6
JournalNeuron
Volume99
Issue number3
DOIs
StatePublished - Aug 8 2018

Fingerprint

Pruritus
MicroRNAs
Lymphoma
Ion Channels
S 6
Intradermal Injections
Cheek
Sensory Receptor Cells
Computer Simulation
Perfusion
Biomarkers
Neurons
Pain
Skin
Peptides
Serum
Neoplasms

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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 ; Liu, Di ; Convertino, Marino ; Wang, Zilong ; Jiang, Changyu ; Kim, Yong Ho ; Luo, Xin ; Zhang, Xin ; Nackley, Andrea ; Dokholyan, Nikolay V. ; Ji, Ru Rong. / miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. In: Neuron. 2018 ; Vol. 99, No. 3. pp. 449-463.e6.
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abstract = "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. How extracellular miRNA signals is unclear. Han et al. describe that miRNA-711, secreted from inoculated lymphoma cells on the back skin, binds TRPA1 ion channels extracellularly on pruriceptive neurons to drive acute and chronic itch via specific core sequence.",
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Han, Q, Liu, D, Convertino, M, Wang, Z, Jiang, C, Kim, YH, Luo, X, Zhang, X, Nackley, A, Dokholyan, NV & Ji, RR 2018, 'miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus', Neuron, vol. 99, no. 3, pp. 449-463.e6. https://doi.org/10.1016/j.neuron.2018.06.039

miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus. / Han, Qingjian; Liu, Di; Convertino, Marino; Wang, Zilong; Jiang, Changyu; Kim, Yong Ho; Luo, Xin; Zhang, Xin; Nackley, Andrea; Dokholyan, Nikolay V.; Ji, Ru Rong.

In: Neuron, Vol. 99, No. 3, 08.08.2018, p. 449-463.e6.

Research output: Contribution to journalArticle

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AU - Han, Qingjian

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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. https://doi.org/10.1016/j.neuron.2018.06.039