A Neuronal piRNA Pathway Inhibits Axon Regeneration in &ITC&IT. &ITelegans&IT

被引:54
作者
Kim, Kyung Won [1 ]
Tang, Ngang Heok [1 ]
Andrusiak, Matthew G. [1 ]
Wu, Zilu [1 ]
Chisholm, Andrew D. [1 ]
Jin, Yishi [1 ,2 ]
机构
[1] Univ Calif San Diego, Div Biol Sci, Sect Neurobiol, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
关键词
CAENORHABDITIS-ELEGANS; C; ELEGANS; SLICER ACTIVITY; EPIGENETIC MEMORY; CRYSTAL-STRUCTURE; NERVOUS-SYSTEM; NONCODING RNAS; PIWI; GERMLINE; BIOGENESIS;
D O I
10.1016/j.neuron.2018.01.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The PIWI-interacting RNA (piRNA) pathway has long been thought to function solely in the germline, but evidence for its functions in somatic cells is emerging. Here we report an unexpected role for the piRNA pathway in Caenorhabditis elegans sensory axon regeneration after injury. Loss of function in a subset of components of the piRNA pathway results in enhanced axon regrowth. Two essential piRNA factors, PRDE-1 and PRG-1/PIWI, inhibit axon regeneration in a gonad-independent and cell-autonomous manner. By smFISH analysis we find that prde-1 transcripts are present in neurons, as well as germ cells. The piRNA pathway inhibits axon regrowth independent of nuclear transcriptional silencing but dependent on the slicer domain of PRG-1/PIWI, suggesting that post-transcriptional gene silencing is involved. Our results reveal the neuronal piRNA pathway as a novel intrinsic repressor of axon regeneration.
引用
收藏
页码:511 / +
页数:15
相关论文
共 51 条
[31]   The tubulin repertoire of Caenorhabditis elegans sensory neurons and its context-dependent role in process outgrowth [J].
Lockhead, Dean ;
Schwarz, Erich M. ;
O'Hagan, Robert ;
Bellotti, Sebastian ;
Krieg, Michael ;
Barr, Maureen M. ;
Dunn, Alexander R. ;
Sternberg, Paul W. ;
Goodman, Miriam B. .
MOLECULAR BIOLOGY OF THE CELL, 2016, 27 (23) :3717-3728
[32]   EFFICIENT GENE-TRANSFER IN C-ELEGANS - EXTRACHROMOSOMAL MAINTENANCE AND INTEGRATION OF TRANSFORMING SEQUENCES [J].
MELLO, CC ;
KRAMER, JM ;
STINCHCOMB, D ;
AMBROS, V .
EMBO JOURNAL, 1991, 10 (12) :3959-3970
[33]   Roles for small noncoding RNAs in silencing of retrotransposons in the mammalian brain [J].
Nandi, Sayan ;
Chandramohan, Dhruva ;
Fioriti, Luana ;
Melnick, Ari M. ;
Hebert, Jean M. ;
Mason, Christopher E. ;
Rajasethupathy, Priyamvada ;
Kandel, Eric R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (45) :12697-12702
[34]   Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity [J].
Parker, JS ;
Roe, SM ;
Barford, D .
EMBO JOURNAL, 2004, 23 (24) :4727-4737
[35]   Transposition-Driven Genomic Heterogeneity in the Drosophila Brain [J].
Perrat, Paola N. ;
DasGupta, Shamik ;
Wang, Jie ;
Theurkauf, William ;
Weng, Zhiping ;
Rosbash, Michael ;
Waddell, Scott .
SCIENCE, 2013, 340 (6128) :91-95
[36]  
Phay M., 2016, MOL NEUROBIOL
[37]   Imaging individual mRNA molecules using multiple singly labeled probes [J].
Raj, Arjun ;
van den Bogaard, Patrick ;
Rifkin, Scott A. ;
van Oudenaarden, Alexander ;
Tyagi, Sanjay .
NATURE METHODS, 2008, 5 (10) :877-879
[38]   A Role for Neuronal piRNAs in the Epigenetic Control of Memory-Related Synaptic Plasticity [J].
Rajasethupathy, Priyamvada ;
Antonov, Igor ;
Sheridan, Robert ;
Frey, Sebastian ;
Sander, Chris ;
Tuschl, Thomas ;
Kandel, Eric R. .
CELL, 2012, 149 (03) :693-707
[39]   Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing [J].
Reuter, Michael ;
Berninger, Philipp ;
Chuma, Shinichiro ;
Shah, Hardik ;
Hosokawa, Mihoko ;
Funaya, Charlotta ;
Antony, Claude ;
Sachidanandam, Ravi ;
Pillai, Ramesh S. .
NATURE, 2011, 480 (7376) :264-U154
[40]   PIWI proteins and PIWI-interacting RNAs in the soma [J].
Ross, Robert J. ;
Weiner, Molly M. ;
Lin, Haifan .
NATURE, 2014, 505 (7483) :353-359