Hormonal regulation of Drosophila microRNA let-7 and miR-125 that target innate immunity.
The steroid 20-hydroxy-ecdysone (20-HE) and the sesquiterpenoid Juvenile Hormone (JH) coordinate insect life stage transitions. 20-HE exerts these effects by the sequential induction of response genes. In the nematode Caenorhabditis elegans hormones also play a role in such transitions, but notably, microRNA such as let-7 and lin-4 have likewise been found to help order developmental steps. Little is known about the corresponding function of homologous microRNA in Drosophila melanogaster, and the way microRNA might be regulated by 20-HE in the fly is ambiguous. Here we used Drosophila S2 cells to analyze the effects of 20-HE on D. melanogaster microRNA let-7 and miR-125, the homolog of lin-4. The induction by 20-HE of let-7 and miR-125 in S2 cells is inhibited by RNAi knockdown of the ecdysone receptor and, as previously shown, by knockdown of its cofactor broad-complex C. To help resolve the currently ambiguous role of 20-HE in the control of microRNA, we show that nanomolar concentrations of 20-HE primes cells to subsequently express microRNA when exposed to micromolar levels of 20-HE. We then explore the role microRNA plays in the established relationship between 20-HE and the induction of innate immunity. We show that the 3'UTR of the antimicrobial peptide diptericin has a let-7 binding site and that let-7 represses translation from this site. We conclude that 20-HE facilitates the initial expression of innate immunity while it simultaneously induces negative regulation via microRNA control of antimicrobial peptide translation.
Garbuzov
Alina
A
Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, USA.
Tatar
Marc
M
D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D004331:Drosophila melanogaster / Q000276:immunology / Q000378:metabolism*; D004441:Ecdysterone / Q000494:pharmacology*; D007113:Immunity, Innate / Q000235:genetics*; D035683:MicroRNAs / Q000187:drug effects / Q000378:metabolism*; D034622:RNA Interference; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors
D029721:Drosophila Proteins; C531976:Let-7 microRNA, Drosophila; C531977:MIRN125 microRNA, Drosophila; D035683:MicroRNAs; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004441:Ecdysterone
Dev Biol. 2002 Apr 1;244(1):170-9
11900466
Nature. 2000 Feb 24;403(6772):901-6
10706289
Aging Cell. 2006 Dec;5(6):533-43
17129215
Receptor. 1993 Fall;3(3):203-9
8167571
Insect Mol Biol. 2005 Dec;14(6):645-52
16313564
Dev Dyn. 2008 Jan;237(1):196-208
18069688
Cold Spring Harb Symp Quant Biol. 2006;71:149-56
17381291
Genome Res. 2007 Dec;17(12):1850-64
17989254
Mol Cell. 2009 Oct 23;36(2):340-7
19854141
Nature. 2004 Sep 16;431(7006):350-5
15372042
Cell Mol Life Sci. 2007 Aug;64(15):1945-58
17558467
Immunity. 1999 Mar;10(3):387-98
10204494
J Immunol. 2007 Oct 15;179(8):5082-9
17911593
Cell. 2004 Jan 23;116(2):281-97
14744438
Cell. 2009 Jan 9;136(1):26-36
19135886
Dev Biol. 2003 Jul 1;259(1):9-18
12812784
Nat Rev Immunol. 2008 Feb;8(2):120-30
18204468
Curr Biol. 2008 Jul 8;18(13):943-50
18571409
Genes Dev. 2006 Oct 15;20(20):2769-72
17043305
Aging Cell. 2005 Apr;4(2):103-8
15771614
J Exp Biol. 2008 Aug;211(Pt 16):2712-24
18689425
Methods Mol Biol. 2008;420:391-424
18641962
Nat Rev Mol Cell Biol. 2005 May;6(5):376-85
15852042
Nature. 2000 Nov 2;408(6808):86-9
11081512
Nat Genet. 2007 Oct;39(10):1278-84
17893677
EMBO J. 1992 Nov;11(11):4083-93
1382981
Genes Dev. 2007 Sep 15;21(18):2277-82
17761811
Cell. 1993 Dec 3;75(5):843-54
8252621
Bioessays. 2003 Oct;25(10):994-1001
14505366
Annu Rev Cell Dev Biol. 2007;23:175-205
17506695
Genes Dev. 2000 Oct 1;14(19):2461-71
11018014
BMC Genomics. 2005 Jun 08;6:88
15943864
Dev Biol. 2003 Jul 1;259(1):1-8
12812783
Genome Res. 2009 Jun;19(6):1006-13
19237466
Insect Biochem Mol Biol. 1996 Feb;26(2):155-60
8882658