The MicroRNA Inhibits Calcium Signaling by Targeting the TIR-1/Sarm1 Adaptor Protein to Control Stochastic L/R Neuronal Asymmetry in
The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWCON and AWCOFF, by inhibiting a calcium-mediated signaling pathway in the future AWCON cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWCON fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWCON cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWCON identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWCON neurons. tir-1 expression is downregulated through its 3′ UTR in AWCON, in which mir-71 is expressed at a higher level than in AWCOFF. In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3′ UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWCON identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation.
Vyšlo v časopise:
The MicroRNA Inhibits Calcium Signaling by Targeting the TIR-1/Sarm1 Adaptor Protein to Control Stochastic L/R Neuronal Asymmetry in. PLoS Genet 8(8): e32767. doi:10.1371/journal.pgen.1002864
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002864
Souhrn
The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWCON and AWCOFF, by inhibiting a calcium-mediated signaling pathway in the future AWCON cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWCON fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWCON cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWCON identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWCON neurons. tir-1 expression is downregulated through its 3′ UTR in AWCON, in which mir-71 is expressed at a higher level than in AWCOFF. In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3′ UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWCON identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation.
Zdroje
1. JohnstonRJJrOtakeYSoodPVogtNBehniaR 2011 Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye. Cell 145 956 968
2. JukamDDesplanC 2010 Binary fate decisions in differentiating neurons. Curr Opin Neurobiol 20 6 13
3. JohnstonRJJrDesplanC 2008 Stochastic neuronal cell fate choices. Curr Opin Neurobiol 18 20 27
4. HobertO 2010 Neurogenesis in the nematode Caenorhabditis elegans. WormBook 1 24
5. YooASGreenwaldI 2005 LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science 310 1330 1333
6. GrandbarbeLBouissacJRandMHrabe de AngelisMArtavanis-TsakonasS 2003 Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process. Development 130 1391 1402
7. MacDonaldHRWilsonARadtkeF 2001 Notch1 and T-cell development: insights from conditional knockout mice. Trends Immunol 22 155 160
8. ChangSJohnstonRJJrFrokjaer-JensenCLockerySHobertO 2004 MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature 430 785 789
9. JohnstonRJHobertO 2003 A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426 845 849
10. JohnstonRJJrHobertO 2005 A novel C. elegans zinc finger transcription factor, lsy-2, required for the cell type-specific expression of the lsy-6 microRNA. Development 132 5451 5460
11. PooleRJHobertO 2006 Early embryonic programming of neuronal left/right asymmetry in C. elegans. Curr Biol 16 2279 2292
12. TroemelERSagastiABargmannCI 1999 Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans. Cell 99 387 398
13. Bauer HuangSLSahekiYVanHovenMKTorayamaIIshiharaT 2007 Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans. Neural Dev 2 24
14. ColosimoMEBrownAMukhopadhyaySGabelCLanjuinAE 2004 Identification of thermosensory and olfactory neuron-specific genes via expression profiling of single neuron types. Curr Biol 14 2245 2251
15. WesPDBargmannCI 2001 C. elegans odour discrimination requires asymmetric diversity in olfactory neurons. Nature 410 698 701
16. ChuangCFBargmannCI 2005 A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev 19 270 281
17. WhiteJGSouthgateEThomsonJNBrennerS 1986 The structure of the nervous system of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314 1 340
18. ChuangCFVanhovenMKFetterRDVerselisVKBargmannCI 2007 An innexin-dependent cell network establishes left-right neuronal asymmetry in C. elegans. Cell 129 787 799
19. VanHovenMKBauer HuangSLAlbinSDBargmannCI 2006 The claudin superfamily protein nsy-4 biases lateral signaling to generate left-right asymmetry in C. elegans olfactory neurons. Neuron 51 291 302
20. LeschBJBargmannCI 2010 The homeodomain protein hmbx-1 maintains asymmetric gene expression in adult C. elegans olfactory neurons. Genes Dev 24 1802 1815
21. LeschBJGehrkeARBulykMLBargmannCI 2009 Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans. Genes Dev 23 345 358
22. ChangCHsiehYWLeschBJBargmannCIChuangCF 2011 Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans. Development 138 3509 3518
23. TaylorRWHsiehYWGamseJTChuangCF 2010 Making a difference together: reciprocal interactions in C. elegans and zebrafish asymmetric neural development. Development 137 681 691
24. WelkerNCHabigJWBassBL 2007 Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes. Rna 13 1090 1102
25. SagastiAHisamotoNHyodoJTanaka-HinoMMatsumotoK 2001 The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates. Cell 105 221 232
26. Tanaka-HinoMSagastiAHisamotoNKawasakiMNakanoS 2002 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans. EMBO Rep 3 56 62
27. BartelDP 2004 MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 281 297
28. GrishokAPasquinelliAEConteDLiNParrishS 2001 Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106 23 34
29. BigelowHRWenickASWongAHobertO 2004 CisOrtho: a program pipeline for genome-wide identification of transcription factor target genes using phylogenetic footprinting. BMC Bioinformatics 5 27
30. KentWJZahlerAM 2000 Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C. elegans genomic alignment. Genome Res 10 1115 1125
31. EnrightAJJohnBGaulUTuschlTSanderC 2003 MicroRNA targets in Drosophila. Genome Biol 5 R1
32. Griffiths-JonesSGrocockRJvan DongenSBatemanAEnrightAJ 2006 miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34 D140 144
33. Griffiths-JonesSSainiHKvan DongenSEnrightAJ 2008 miRBase: tools for microRNA genomics. Nucleic Acids Res 36 D154 158
34. GrimsonAFarhKKJohnstonWKGarrett-EngelePLimLP 2007 MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27 91 105
35. LallSGrunDKrekAChenKWangYL 2006 A genome-wide map of conserved microRNA targets in C. elegans. Curr Biol 16 460 471
36. HammellMLongDZhangLLeeACarmackCS 2008 mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts. Nat Methods 5 813 819
37. AbbottALAlvarez-SaavedraEMiskaEALauNCBartelDP 2005 The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev Cell 9 403 414
38. Alvarez-SaavedraEHorvitzHR 2010 Many families of C. elegans microRNAs are not essential for development or viability. Curr Biol 20 367 373
39. BrennerJLJasiewiczKLFahleyAFKempBJAbbottAL 2010 Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans. Curr Biol 20 1321 1325
40. MiskaEAAlvarez-SaavedraEAbbottALLauNCHellmanAB 2007 Most Caenorhabditis elegans microRNAs are individually not essential for development or viability. PLoS Genet 3 e215 doi:10.1371/journal.pgen.0030215
41. RoayaieKCrumpJGSagastiABargmannCI 1998 The G alpha protein ODR-3 mediates olfactory and nociceptive function and controls cilium morphogenesis in C. elegans olfactory neurons. Neuron 20 55 67
42. LiXCarthewRW 2005 A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye. Cell 123 1267 1277
43. HanXGomesJEBirminghamCLPintardLSugimotoA 2009 The role of protein phosphatase 4 in regulating microtubule severing in the Caenorhabditis elegans embryo. Genetics 181 933 943
44. ChenJKastanMB 2010 5′-3′-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage. Genes & development 24 2146 2156
45. FranchTGultyaevAPGerdesK 1997 Programmed cell death by hok/sok of plasmid R1: processing at the hok mRNA 3′-end triggers structural rearrangements that allow translation and antisense RNA binding. Journal of molecular biology 273 38 51
46. EdgilDHarrisE 2006 End-to-end communication in the modulation of translation by mammalian RNA viruses. Virus research 119 43 51
47. BouliasKHorvitzHR 2012 The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO. Cell metabolism 15 439 450
48. IsikMKorswagenHCBerezikovE 2010 Expression patterns of intronic microRNAs in Caenorhabditis elegans. Silence 1 5
49. MartinezNJOwMCReece-HoyesJSBarrasaMIAmbrosVR 2008 Genome-scale spatiotemporal analysis of Caenorhabditis elegans microRNA promoter activity. Genome Res 18 2005 2015
50. KratsiosPStolfiALevineMHobertO 2011 Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene. Nat Neurosci
51. LanjuinAVanHovenMKBargmannCIThompsonJKSenguptaP 2003 Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans. Dev Cell 5 621 633
52. ZhangSMaCChalfieM 2004 Combinatorial marking of cells and organelles with reconstituted fluorescent proteins. Cell 119 137 144
53. HammellCMLubinIBoagPRBlackwellTKAmbrosV 2009 nhl-2 Modulates microRNA activity in Caenorhabditis elegans. Cell 136 926 938
54. ChenCRidzonDABroomerAJZhouZLeeDH 2005 Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33 e179
55. JohnstonRJJrChangSEtchbergerJFOrtizCOHobertO 2005 MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc Natl Acad Sci U S A 102 12449 12454
56. de LencastreAPincusZZhouKKatoMLeeSS 2010 MicroRNAs both promote and antagonize longevity in C. elegans. Curr Biol 20 2159 2168
57. PincusZSmith-VikosTSlackFJ 2011 MicroRNA predictors of longevity in Caenorhabditis elegans. PLoS Genet 7 e1002306 doi:10.1371/journal.pgen.1002306
58. KarpXHammellMOwMCAmbrosV 2011 Effect of life history on microRNA expression during C. elegans development. Rna 17 639 651
59. KatoMde LencastreAPincusZSlackFJ 2009 Dynamic expression of small non-coding RNAs, including novel microRNAs and piRNAs/21U-RNAs, during Caenorhabditis elegans development. Genome Biol 10 R54
60. ZhangXZabinskyRTengYCuiMHanM 2011 microRNAs play critical roles in the survival and recovery of Caenorhabditis elegans from starvation-induced L1 diapause. Proceedings of the National Academy of Sciences of the United States of America 108 17997 18002
61. LiberatiNTFitzgeraldKAKimDHFeinbaumRGolenbockDT 2004 Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proceedings of the National Academy of Sciences of the United States of America 101 6593 6598
62. BartelDP 2009 MicroRNAs: target recognition and regulatory functions. Cell 136 215 233
63. AmbrosV 2004 The functions of animal microRNAs. Nature 431 350 355
64. ChenCZLiLLodishHFBartelDP 2004 MicroRNAs modulate hematopoietic lineage differentiation. Science 303 83 86
65. ZhaoZBoyleTJLiuZMurrayJIWoodWB 2010 A negative regulatory loop between microRNA and Hox gene controls posterior identities in Caenorhabditis elegans. PLoS Genet 6 e1001089 doi:10.1371/journal.pgen.1001089
66. RubyJGJanCPlayerCAxtellMJLeeW 2006 Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127 1193 1207
67. Ibanez-VentosoCVoraMDriscollM 2008 Sequence relationships among C. elegans, D. melanogaster and human microRNAs highlight the extensive conservation of microRNAs in biology. PLoS ONE 3 e2818 doi:10.1371/journal.pone.0002818
68. Lagos-QuintanaMRauhutRMeyerJBorkhardtATuschlT 2003 New microRNAs from mouse and human. RNA 9 175 179
69. LimLPLauNCWeinsteinEGAbdelhakimAYektaS 2003 The microRNAs of Caenorhabditis elegans. Genes Dev 17 991 1008
70. AllenRSLiJStahleMIDubroueAGublerF 2007 Genetic analysis reveals functional redundancy and the major target genes of the Arabidopsis miR159 family. Proc Natl Acad Sci U S A 104 16371 16376
71. CimminoACalinGAFabbriMIorioMVFerracinM 2005 miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102 13944 13949
72. LinsleyPSSchelterJBurchardJKibukawaMMartinMM 2007 Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol 27 2240 2252
73. ShawWRArmisenJLehrbachNJMiskaEA 2010 The conserved miR-51 microRNA family is redundantly required for embryonic development and pharynx attachment in Caenorhabditis elegans. Genetics 185 897 905
74. VenturaAYoungAGWinslowMMLintaultLMeissnerA 2008 Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132 875 886
75. ChatterjeeSGrosshansH 2009 Active turnover modulates mature microRNA activity in Caenorhabditis elegans. Nature 461 546 549
76. BerridgeMJLippPBootmanMD 2000 The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1 11 21
77. BasuBBruecknerM 2008 Cilia multifunctional organelles at the center of vertebrate left-right asymmetry. Curr Top Dev Biol 85 151 174
78. ChengHYPappJWVarlamovaODziemaHRussellB 2007 microRNA modulation of circadian-clock period and entrainment. Neuron 54 813 829
79. FavereauxAThoumineOBouali-BenazzouzRRoquesVPaponMA 2011 Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. EMBO J
80. IkedaSHeAKongSWLuJBejarR 2009 MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol 29 2193 2204
81. LiuXZhanZXuLMaFLiD 2010 MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIalpha. J Immunol 185 7244 7251
82. BrennerS 1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94
83. TursunBPatelTKratsiosPHobertO 2011 Direct conversion of C. elegans germ cells into specific neuron types. Science 331 304 308
84. MelloCFireA 1995 DNA transformation. Methods Cell Biol 48 451 482
85. LivakKJSchmittgenTD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25 402 408
86. DidianoDCochellaLTursunBHobertO 2010 Neuron-type specific regulation of a 3′UTR through redundant and combinatorially acting cis-regulatory elements. Rna 16 349 363
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 8
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes
- It's All in the Timing: Too Much E2F Is a Bad Thing
- The PARN Deadenylase Targets a Discrete Set of mRNAs for Decay and Regulates Cell Motility in Mouse Myoblasts
- Novel Loci for Metabolic Networks and Multi-Tissue Expression Studies Reveal Genes for Atherosclerosis