Downregulation of the Host Gene by miR-92 Is Essential for Neuroblast Self-Renewal in


Animal development is regulated by many genes including a class of small RNAs called microRNAs (miRNAs). Nearly half of the miRNAs are located in the protein coding genes but functional importance of this genomic organization is unclear. Here we use Drosophila stem cells in the brain as a model system to investigate the interactions between miR-92a and miR-92b and their host gene jing interacting regulatory protein 1 (jigr1). Our studies reveal that these miRNAs prevent premature differentiation of neural stem cells and they do so in part through directly targeting and suppressing their host gene, jigr1. Our results reveal a novel function of the miR-92 family and identify another negative feedback loop as an essential regulator in neural stem cell development.


Vyšlo v časopise: Downregulation of the Host Gene by miR-92 Is Essential for Neuroblast Self-Renewal in. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005264
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005264

Souhrn

Animal development is regulated by many genes including a class of small RNAs called microRNAs (miRNAs). Nearly half of the miRNAs are located in the protein coding genes but functional importance of this genomic organization is unclear. Here we use Drosophila stem cells in the brain as a model system to investigate the interactions between miR-92a and miR-92b and their host gene jing interacting regulatory protein 1 (jigr1). Our studies reveal that these miRNAs prevent premature differentiation of neural stem cells and they do so in part through directly targeting and suppressing their host gene, jigr1. Our results reveal a novel function of the miR-92 family and identify another negative feedback loop as an essential regulator in neural stem cell development.


Zdroje

1. Ambros V. microRNAs: tiny regulators with great potential. Cell [Internet]. 2001 Dec 28 [cited 2014 Sep 19];107(7):823–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11779458 11779458

2. Ebert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell [Internet]. 2012 Apr 27 [cited 2014 Jul 9];149(3):515–24. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3351105&tool=pmcentrez&rendertype=abstract doi: 10.1016/j.cell.2012.04.005 22541426

3. Newman M a, Hammond SM. Emerging paradigms of regulated microRNA processing. Genes Dev [Internet]. 2010 Jun 1 [cited 2014 Jun 5];24(11):1086–92. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2878647&tool=pmcentrez&rendertype=abstract doi: 10.1101/gad.1919710 20516194

4. Kim Y-K, Kim VN. Processing of intronic microRNAs. EMBO J [Internet]. 2007 Feb 7 [cited 2014 Aug 14];26(3):775–83. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1794378&tool=pmcentrez&rendertype=abstract 17255951

5. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res [Internet]. 2004 Oct [cited 2014 Jul 9];14(10A):1902–10. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=524413&tool=pmcentrez&rendertype=abstract 15364901

6. Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA [Internet]. 2005 Mar [cited 2014 Aug 27];11(3):241–7. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1370713&tool=pmcentrez&rendertype=abstract 15701730

7. He C, Li Z, Chen P, Huang H, Hurst LD, Chen J. Young intragenic miRNAs are less coexpressed with host genes than old ones: implications of miRNA-host gene coevolution. Nucleic Acids Res [Internet]. 2012 May [cited 2014 Sep 24];40(9):4002–12. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3351155&tool=pmcentrez&rendertype=abstract doi: 10.1093/nar/gkr1312 22238379

8. Ramalingam P, Palanichamy JK, Singh A, Das P, Bhagat M, Kassab MA, et al. Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing. RNA [Internet]. 2014 Jan [cited 2014 Jun 2];20(1):76–87. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24226766 doi: 10.1261/rna.041814.113 24226766

9. Hartenstein V, Rudloff E, Campos-Ortega JA. The pattern of proliferation of the neuroblasts in the wild-type embryo of Drosophila melanogaster. Roux’s Arch Dev Biol [Internet]. 1987 Dec [cited 2014 Sep 25];196(8):473–85. Available from: http://link.springer.com/10.1007/BF00399871

10. Truman JW, Bate M. Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol [Internet]. 1988 Jan;125(1):145–57. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3119399 3119399

11. Maurange C, Gould AP. Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila. Trends Neurosci [Internet]. 2005 Jan [cited 2014 Jul 7];28(1):30–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15626494 15626494

12. Jiang Y, Reichert H. Drosophila Neural Stem Cells in Brain Development and Tumor Formation. J Neurogenet [Internet]. 2014 May 12 [cited 2014 Sep 25];1–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24766377

13. Sun X, Morozova T, Sonnenfeld M. Glial and neuronal functions of the Drosophila homolog of the human SWI/SNF gene ATR-X (DATR-X) and the jing zinc-finger gene specify the lateral positioning of longitudinal glia and axons. Genetics [Internet]. 2006 Jul [cited 2014 Jun 11];173(3):1397–415. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1526706&tool=pmcentrez&rendertype=abstract 16648585

14. Egger B, Boone JQ, Stevens NR, Brand AH, Doe CQ. Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe. Neural Dev [Internet]. 2007 Jan [cited 2012 Aug 30];2(January):1. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1779784&tool=pmcentrez&rendertype=abstract

15. Parks AL, Cook KR, Belvin M, Dompe NA, Fawcett R, Huppert K, et al. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet [Internet]. 2004 Mar [cited 2014 Jul 14];36(3):288–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14981519 14981519

16. Huang J, Zhou W, Dong W, Watson AM, Hong Y. From the Cover: Directed, efficient, and versatile modifications of the Drosophila genome by genomic engineering. Proc Natl Acad Sci U S A [Internet]. 2009 May 19 [cited 2014 Sep 15];106(20):8284–9. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2688891&tool=pmcentrez&rendertype=abstract doi: 10.1073/pnas.0900641106 19429710

17. Chen Z, Liang S, Zhao Y, Han Z. miR-92b regulates Mef2 levels through a negative-feedback circuit during Drosophila muscle development. Development [Internet]. 2012 Oct [cited 2013 Aug 12];139(19):3543–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22899845 doi: 10.1242/dev.082719 22899845

18. Fuse N, Hisata K, Katzen AL, Matsuzaki F. Heterotrimeric G Proteins Regulate Daughter Cell Size Asymmetry in Drosophila Neuroblast Divisions. Curr Biol. 2003;13(15):947–54.

19. Song Y, Lu B. Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila. Genes Dev [Internet]. 2011 Dec 15 [cited 2014 Jun 4];25(24):2644–58. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3248685&tool=pmcentrez&rendertype=abstract doi: 10.1101/gad.171959.111 22190460

20. Xiao Q, Komori H, Lee C-Y. Klumpfuss Distinguishes Stem Cells From Progenitor Cells During Asymmetric Neuroblast Division. Development [Internet]. 2012 Aug [cited 2014 Mar 22];139(15):2670–80. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3392700&tool=pmcentrez&rendertype=abstract doi: 10.1242/dev.081687 22745313

21. Maurange C, Cheng L, Gould AP. Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell [Internet]. 2008 May 30 [cited 2014 Jun 7];133(5):891–902. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18510932 doi: 10.1016/j.cell.2008.03.034 18510932

22. Lai S-L, Doe CQ. Transient nuclear Prospero induces neural progenitor quiescence. Elife [Internet]. 2014 Jan [cited 2015 Jan 31];3:1–12. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4212206&tool=pmcentrez&rendertype=abstract doi: 10.7554/eLife.03363 25354199

23. Lee T, Luo L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron [Internet]. 1999 Mar;22(3):451–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10197526 10197526

24. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell [Internet]. 2009 Jan 23 [cited 2014 Jul 9];136(2):215–33. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3794896&tool=pmcentrez&rendertype=abstract doi: 10.1016/j.cell.2009.01.002 19167326

25. Hinske LCG, Galante P a F, Kuo WP, Ohno-Machado L. A potential role for intragenic miRNAs on their hosts’ interactome. BMC Genomics [Internet]. 2010 Jan;11:533. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3091682&tool=pmcentrez&rendertype=abstract doi: 10.1186/1471-2164-11-533 20920310

26. Liu M, Roth A, Yu M, Morris R, Bersani F, Rivera MN, et al. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes Dev [Internet]. 2013 Dec 1 [cited 2014 Jun 11];27(23):2543–8. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3861668&tool=pmcentrez&rendertype=abstract doi: 10.1101/gad.224170.113 24298054

27. Kos A, Olde Loohuis NFM, Wieczorek ML, Glennon JC, Martens GJM, Kolk SM, et al. A potential regulatory role for intronic microRNA-338-3p for its host gene encoding apoptosis-associated tyrosine kinase. PLoS One [Internet]. 2012 Jan [cited 2014 Jun 30];7(2):e31022. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3281898&tool=pmcentrez&rendertype=abstract doi: 10.1371/journal.pone.0031022 22363537

28. Dill H, Linder B, Fehr A, Fischer U. Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2. Genes Dev [Internet]. 2012 Jan 1 [cited 2014 Jun 14];26(1):25–30. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3258962&tool=pmcentrez&rendertype=abstract doi: 10.1101/gad.177774.111 22215807

29. Cao G, Huang B, Liu Z, Zhang J, Xu H, Xia W, et al. Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways. Biochem Biophys Res Commun [Internet]. Elsevier Inc.; 2010 Jun 11 [cited 2014 Jun 30];396(4):978–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20470754 doi: 10.1016/j.bbrc.2010.05.037 20470754

30. Zhu Y, Lu Y, Zhang Q, Liu J, Li T, Yang J, et al. MicroRNA-26a / b and their host genes cooperate to inhibit the G1 / S transition by activating the pRb protein. Nucleic Acids Res. 2012;40(10):4615–25. doi: 10.1093/nar/gkr1278 22210897

31. Zhou H, Rigoutsos I. MiR-103a-3p targets the 5 ′ UTR of GPRC5A in pancreatic cells. RNA. 2014;20:1–9. doi: 10.1261/rna.038182.113 24255166

32. Barik S. An intronic microRNA silences genes that are functionally antagonistic to its host gene. Nucleic Acids Res. 2008;36(16):5232–41. doi: 10.1093/nar/gkn513 18684991

33. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell [Internet]. 2007 Jul 13 [cited 2014 May 24];130(1):89–100. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2729315&tool=pmcentrez&rendertype=abstract 17599402

34. Sundaram GM, Common JEA, Gopal FE, Srikanta S, Lakshman K, Lunny DP, et al. “See-saw” expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature [Internet]. 2013 Mar 7 [cited 2014 Jul 12];495(7439):103–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23395958 doi: 10.1038/nature11890 23395958

35. Bian S, Hong J, Li Q, Schebelle L, Pollock A, Knauss JL, et al. MicroRNA cluster miR-17-92 regulates neural stem cell expansion and transition to intermediate progenitors in the developing mouse neocortex. Cell Rep [Internet]. The Authors; 2013 May 30 [cited 2014 Jan 22];3(5):1398–406. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23623502 doi: 10.1016/j.celrep.2013.03.037 23623502

36. Nowakowski TJ, Fotaki V, Pollock A, Sun T, Pratt T, Price DJ. MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain. 2013;1–6.

37. Fei J-F, Haffner C, Huttner WB. 3’ UTR-dependent, miR-92-mediated restriction of Tis21 expression maintains asymmetric neural stem cell division to ensure proper neocortex size. Cell Rep [Internet]. The Authors; 2014 Apr 24 [cited 2014 Jun 6];7(2):398–411. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24726360 doi: 10.1016/j.celrep.2014.03.033 24726360

38. Scotto-Lavino E, Du G, Frohman M a. 3’ end cDNA amplification using classic RACE. Nat Protoc [Internet]. 2006 Jan [cited 2015 Feb 26];1(6):2742–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17406530 17406530

39. Li Z, Lu Y, Xu X-L, Gao F-B. The FTD/ALS-associated RNA-binding protein TDP-43 regulates the robustness of neuronal specification through microRNA-9a in Drosophila. Hum Mol Genet [Internet]. 2013 Jan 15 [cited 2014 Sep 25];22(2):218–25. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3526156&tool=pmcentrez&rendertype=abstract doi: 10.1093/hmg/dds420 23042786

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 5
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa