Hypothalamic miR-30 regulates puberty onset via repression of the puberty-suppressing factor, Mkrn3

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art_HERAS_Hypothalamic_miR30_regulates_puberty_onset_via_repression_of_2019.PDF (2 MB)
Citações na Scopus
48
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
HERAS, Violeta
SANGIAO-ALVARELLOS, Susana
MANFREDI-LOZANO, Maria
SANCHEZ-TAPIA, Maria J.
RUIZ-PINO, Francisco
ROA, Juan
LARA-CHICA, Maribel
MORRUGARES-CARMONA, Rosario
JOUY, Nathalie
ABREU, Ana P.
Citação
PLOS BIOLOGY, v.17, n.11, article ID e3000532, 24p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Mkrn3, the maternally imprinted gene encoding the makorin RING-finger protein-3, has recently emerged as putative pubertal repressor, as evidenced by central precocity caused by MKRN3 mutations in humans; yet, the molecular underpinnings of this key regulatory action remain largely unexplored. We report herein that the microRNA, miR-30, with three binding sites in a highly conserved region of its 3 ' UTR, operates as repressor of Mkrn3 to control pubertal onset. Hypothalamic miR-30b expression increased, while Mkrn3 mRNA and protein content decreased, during rat postnatal maturation. Neonatal estrogen exposure, causing pubertal alterations, enhanced hypothalamic Mkrn3 and suppressed miR-30b expression in female rats. Functional in vitro analyses demonstrated a strong repressive action of miR-30b on Mkrn3 3 ' UTR. Moreover, central infusion during the juvenile period of target site blockers, tailored to prevent miR-30 binding to Mkrn3 3 ' UTR, reversed the prepubertal down-regulation of hypothalamic Mkrn3 protein and delayed female puberty. Collectively, our data unveil a novel hypothalamic miRNA pathway, involving miR-30, with a prominent role in the control of puberty via Mkrn3 repression. These findings expand our current understanding of the molecular basis of puberty and its disease states.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/34273
Referências
  1. Abreu AP, 2016, LANCET DIABETES ENDO, V4, P254, DOI 10.1016/S2213-8587(15)00418-0
  2. Abreu AP, 2015, J MOL ENDOCRINOL, V54, pR131, DOI 10.1530/JME-14-0315
  3. Abreu AP, 2013, NEW ENGL J MED, V368, P2467, DOI 10.1056/NEJMoa1302160
  4. Avendano S, 2017, HUM REPROD UPDATE, V23, P737, DOI 10.1093/humupd/dmx025
  5. Bessa DS, 2017, NEUROENDOCRINOLOGY, V105, P17, DOI 10.1159/000446963
  6. Bhat-Nakshatri P, 2009, NUCLEIC ACIDS RES, V37, P4850, DOI 10.1093/nar/gkp500
  7. Boullu-Ciocca S, 2005, DIABETES, V54, P197, DOI 10.2337/diabetes.54.1.197
  8. Busch AS, 2016, J CLIN ENDOCR METAB, V101, P2588, DOI 10.1210/jc.2016-1488
  9. Castellano JM, 2016, ENDOCR DEV, V29, P87, DOI 10.1159/000438877
  10. Castellano JM, 2011, ENDOCRINOLOGY, V152, P3396, DOI 10.1210/en.2010-1415
  11. Enright AJ, 2004, GENOME BIOL, V5
  12. Gaytan F, 2017, SCI REP-UK, V7, DOI 10.1038/srep46381
  13. Gottsch ML, 2011, ENDOCRINOLOGY, V152, P4298, DOI 10.1210/en.2011-1521
  14. Hagen CP, 2015, J CLIN ENDOCR METAB, V100, P1920, DOI 10.1210/jc.2014-4462
  15. Herbison AE, 2016, NAT REV ENDOCRINOL, V12, P452, DOI 10.1038/nrendo.2016.70
  16. Jong MTC, 1999, HUM MOL GENET, V8, P795, DOI 10.1093/hmg/8.5.795
  17. Krek A, 2005, NAT GENET, V37, P495, DOI 10.1038/ng1536
  18. Kuokkanen S, 2010, BIOL REPROD, V82, P791, DOI 10.1095/biolreprod.109.081059
  19. Lehman MN, 2010, ENDOCRINOLOGY, V151, P3479, DOI 10.1210/en.2010-0022
  20. Lewis BP, 2005, CELL, V120, P15, DOI 10.1016/j.cell.2004.12.035
  21. Liu HF, 2017, ONCOTARGET, V8, P85102, DOI 10.18632/oncotarget.19347
  22. Lomniczi A, 2016, ENDOCR DEV, V29, P1, DOI 10.1159/000438840
  23. Lomniczi A, 2013, HORM BEHAV, V64, P175, DOI 10.1016/j.yhbeh.2012.09.013
  24. Macedo DB, 2018, NEUROENDOCRINOLOGY, V107, P127, DOI 10.1159/000490059
  25. Mao L, 2018, BIOMED RES INT, DOI 10.1155/2018/9623412
  26. Messina A, 2016, NAT NEUROSCI, V19, P835, DOI 10.1038/nn.4298
  27. Navarro VM, 2009, J NEUROSCI, V29, P11859, DOI 10.1523/JNEUROSCI.1569-09.2009
  28. Navarro VM, 2004, J PHYSIOL-LONDON, V561, P379, DOI 10.1113/jphysiol.2004.072298
  29. Ojeda SR, 2006, KNOBIL AND NEILL'S PHYSIOLOGY OF REPRODUCTION, VOLS 1 AND 2, 3RD EDITON, P2061
  30. Ojeda SR, 2010, ENDOCR DEV, V17, P44, DOI 10.1159/000262527
  31. Ojeda SR, 2006, ENDOCRINOLOGY, V147, P1166, DOI 10.1210/en.2005-1136
  32. PINILLA L, 1993, J REPROD FERTIL, V97, P13, DOI 10.1530/jrf.0.0970013
  33. Pinilla L, 2002, J ENDOCRINOL, V172, P441, DOI 10.1677/joe.0.1720441
  34. Pinilla L, 2011, AM J PHYSIOL-ENDOC M, V300, pE837, DOI 10.1152/ajpendo.00598.2010
  35. ROGERS L C, 1991, Molecular and Cellular Neuroscience, V2, P130, DOI 10.1016/1044-7431(91)90005-9
  36. Sanchez-Garrido MA, 2013, ENDOCRINOLOGY, V154, P3387, DOI 10.1210/en.2012-2157
  37. Sangiao-Alvarellos S, 2013, ENDOCRINOLOGY, V154, P942, DOI 10.1210/en.2012-2006
  38. Sangiao-Alvarellos S, 2014, ENDOCRINOLOGY, V155, P1838, DOI 10.1210/en.2013-1770
  39. Simon D, 2016, EUR J ENDOCRINOL, V174, P1, DOI 10.1530/EJE-15-0488
  40. Tena-Sempere M, 2013, CURR TOP DEV BIOL, V105, P299, DOI 10.1016/B978-0-12-396968-2.00011-7
  41. Treen AK, 2016, MOL ENDOCRINOL, V30, P217, DOI 10.1210/me.2015-1189
  42. Vidal-Gomez X, 2018, CELL PHYSIOL BIOCHEM, V45, P1878, DOI 10.1159/000487910
  43. Viswanathan SR, 2008, SCIENCE, V320, P97, DOI 10.1126/science.1154040
  44. Wang XW, 2008, BIOINFORMATICS, V24, P325, DOI 10.1093/bioinformatics/btm595
  45. Watson P, 2006, RAT BRAIN STEREOTAXI
  46. Xu Y, 2018, EUR REV MED PHARMACO, V22, P5206, DOI 10.26355/eurrev_201808_15718

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/42