A Motor Neuron Protective Role of MiR-969 Mediated by the Transcription Factor Kay

Overview

Journal RNA Biol

Specialty Molecular Biology

Date 2020 May 14

PMID 32397794

Citations 2

Authors

Xiao Zhang

Jialan Lyu

Xiaoye Jin

Weiwei Yang

Ziwei Lou

Yongmei Xi

Xiaohang Yang

Wanzhong Ge

Affiliations

Soon will be listed here.

Abstract

Maintenance of motor neuron structure and function is crucial in development and motor behaviour. However, the genetic regulatory mechanism of motor neuron function remains less well understood. In the present study, we identify a novel neuroprotective role of the microRNA miR-969 in motor neurons. miR-969 is highly expressed in motor neurons. Loss of miR-969 results in early-onset and age-progressive locomotion impairment. Flies lacking miR-969 also exhibit shortened lifespan. Moreover, miR-969 is required in motor neurons. We further identify kay as a functionally important target of miR-969. Together, our results indicate that miR-969 can protect motor neuron function by limiting kay activity in .

Citing Articles

Sexually dimorphic microRNA miR-190 regulates lifespan in male .

Fernandes J, Varghese J RNA Biol. 2022; 19(1):1085-1093.

PMID: 36178157 PMC: 9542781. DOI: 10.1080/15476286.2022.2127544.

A mini-screen to identify the role of microRNAs in the Drosophila Insulin-Producing cells regulating lifespan.

Fernandes J, Varghese J MicroPubl Biol. 2022; 2022.

PMID: 35622513 PMC: 9010116. DOI: 10.17912/micropub.biology.000536.

References

Hawley Z, Campos-Melo D, Droppelmann C, Strong M . MotomiRs: miRNAs in Motor Neuron Function and Disease. Front Mol Neurosci. 2017; 10:127. PMC: 5415563. DOI: 10.3389/fnmol.2017.00127. View

Picao-Osorio J, Johnston J, Landgraf M, Berni J, Alonso C . MicroRNA-encoded behavior in Drosophila. Science. 2015; 350(6262):815-20. PMC: 4902127. DOI: 10.1126/science.aad0217. View

Chen J, Huang Y, Mazzoni E, Tan G, Zavadil J, Wichterle H . Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop. Neuron. 2011; 69(4):721-35. PMC: 3062262. DOI: 10.1016/j.neuron.2011.01.014. View

Ali Y, Escala W, Ruan K, Zhai R . Assaying locomotor, learning, and memory deficits in Drosophila models of neurodegeneration. J Vis Exp. 2011; (49). PMC: 3197301. DOI: 10.3791/2504. View

Fulga T, McNeill E, Binari R, Yelick J, Blanche A, Booker M . A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs. Nat Commun. 2015; 6:7279. PMC: 4471878. DOI: 10.1038/ncomms8279. View

Sanyal S, Narayanan R, Consoulas C, Ramaswami M . Evidence for cell autonomous AP1 function in regulation of Drosophila motor-neuron plasticity. BMC Neurosci. 2003; 4:20. PMC: 201019. DOI: 10.1186/1471-2202-4-20. View

Bartel D . Metazoan MicroRNAs. Cell. 2018; 173(1):20-51. PMC: 6091663. DOI: 10.1016/j.cell.2018.03.006. View

Ruby J, Stark A, Johnston W, Kellis M, Bartel D, Lai E . Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs. Genome Res. 2007; 17(12):1850-64. PMC: 2099593. DOI: 10.1101/gr.6597907. View

Sanyal S, Sandstrom D, Hoeffer C, Ramaswami M . AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila. Nature. 2002; 416(6883):870-4. DOI: 10.1038/416870a. View

10.

Etter P, Narayanan R, Navratilova Z, Patel C, Bohmann D, Jasper H . Synaptic and genomic responses to JNK and AP-1 signaling in Drosophila neurons. BMC Neurosci. 2005; 6:39. PMC: 1175850. DOI: 10.1186/1471-2202-6-39. View

11.

Bushati N, Cohen S . microRNA functions. Annu Rev Cell Dev Biol. 2007; 23:175-205. DOI: 10.1146/annurev.cellbio.23.090506.123406. View

12.

Raouf Issa A, Picao-Osorio J, Rito N, Chiappe M, Alonso C . A Single MicroRNA-Hox Gene Module Controls Equivalent Movements in Biomechanically Distinct Forms of Drosophila. Curr Biol. 2019; 29(16):2665-2675.e4. PMC: 6710004. DOI: 10.1016/j.cub.2019.06.082. View

13.

McNeill E, Van Vactor D . MicroRNAs shape the neuronal landscape. Neuron. 2012; 75(3):363-79. PMC: 3441179. DOI: 10.1016/j.neuron.2012.07.005. View

14.

Guan W, Venkatasubramanian L, Baek M, Mann R, Enriquez J . Visualize Drosophila Leg Motor Neuron Axons Through the Adult Cuticle. J Vis Exp. 2018; (140). PMC: 6544026. DOI: 10.3791/58365. View

15.

Akiyama T, Suzuki N, Ishikawa M, Fujimori K, Sone T, Kawada J . Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons. EBioMedicine. 2019; 45:362-378. PMC: 6642224. DOI: 10.1016/j.ebiom.2019.06.013. View

16.

Chen Y, Song S, Weng R, Verma P, Kugler J, Buescher M . Systematic study of Drosophila microRNA functions using a collection of targeted knockout mutations. Dev Cell. 2014; 31(6):784-800. DOI: 10.1016/j.devcel.2014.11.029. View

17.

Tsurudome K, Tsang K, Liao E, Ball R, Penney J, Yang J . The Drosophila miR-310 cluster negatively regulates synaptic strength at the neuromuscular junction. Neuron. 2010; 68(5):879-93. PMC: 3034365. DOI: 10.1016/j.neuron.2010.11.016. View

18.

Jochum W, Passegue E, Wagner E . AP-1 in mouse development and tumorigenesis. Oncogene. 2001; 20(19):2401-12. DOI: 10.1038/sj.onc.1204389. View

19.

Carthew R, Agbu P, Giri R . MicroRNA function in Drosophila melanogaster. Semin Cell Dev Biol. 2016; 65:29-37. PMC: 5660628. DOI: 10.1016/j.semcdb.2016.03.015. View

20.

Kanning K, Kaplan A, Henderson C . Motor neuron diversity in development and disease. Annu Rev Neurosci. 2010; 33:409-40. DOI: 10.1146/annurev.neuro.051508.135722. View