Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p

Kihoon Han, Vincenzo Alessandro Gennarino, Yoontae Lee, Kaifang Pang, Kazue Hashimoto-Torii, Sanaa Choufani, Chandrasekhar S. Raju, Michael C. Oldham, Rosanna Weksberg, Pasko Rakic, Zhandong Liu, Huda Y. Zoghbi

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.

Original languageEnglish
Pages (from-to)485-490
Number of pages6
JournalGenes and Development
Volume27
Issue number5
DOIs
Publication statusPublished - 2013 Mar 1
Externally publishedYes

Fingerprint

MicroRNAs
Brain
Proteins
Untranslated Regions
Beckwith-Wiedemann Syndrome
Co-Repressor Proteins
Dendritic Spines
Human Development
Fetal Development
Epigenomics
Fibroblasts
Binding Sites
Phenotype
Neurons

Keywords

  • 3' UTR
  • HDAC4
  • Human fetal brain
  • MeCP2
  • miR-483-5p
  • TBL1X

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Han, K., Gennarino, V. A., Lee, Y., Pang, K., Hashimoto-Torii, K., Choufani, S., ... Zoghbi, H. Y. (2013). Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes and Development, 27(5), 485-490. https://doi.org/10.1101/gad.207456.112

Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. / Han, Kihoon; Gennarino, Vincenzo Alessandro; Lee, Yoontae; Pang, Kaifang; Hashimoto-Torii, Kazue; Choufani, Sanaa; Raju, Chandrasekhar S.; Oldham, Michael C.; Weksberg, Rosanna; Rakic, Pasko; Liu, Zhandong; Zoghbi, Huda Y.

In: Genes and Development, Vol. 27, No. 5, 01.03.2013, p. 485-490.

Research output: Contribution to journalArticle

Han, K, Gennarino, VA, Lee, Y, Pang, K, Hashimoto-Torii, K, Choufani, S, Raju, CS, Oldham, MC, Weksberg, R, Rakic, P, Liu, Z & Zoghbi, HY 2013, 'Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p', Genes and Development, vol. 27, no. 5, pp. 485-490. https://doi.org/10.1101/gad.207456.112
Han K, Gennarino VA, Lee Y, Pang K, Hashimoto-Torii K, Choufani S et al. Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. Genes and Development. 2013 Mar 1;27(5):485-490. https://doi.org/10.1101/gad.207456.112
Han, Kihoon ; Gennarino, Vincenzo Alessandro ; Lee, Yoontae ; Pang, Kaifang ; Hashimoto-Torii, Kazue ; Choufani, Sanaa ; Raju, Chandrasekhar S. ; Oldham, Michael C. ; Weksberg, Rosanna ; Rakic, Pasko ; Liu, Zhandong ; Zoghbi, Huda Y. / Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. In: Genes and Development. 2013 ; Vol. 27, No. 5. pp. 485-490.
@article{780c1a0acd0542139314f14f3838818e,
title = "Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p",
abstract = "Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.",
keywords = "3' UTR, HDAC4, Human fetal brain, MeCP2, miR-483-5p, TBL1X",
author = "Kihoon Han and Gennarino, {Vincenzo Alessandro} and Yoontae Lee and Kaifang Pang and Kazue Hashimoto-Torii and Sanaa Choufani and Raju, {Chandrasekhar S.} and Oldham, {Michael C.} and Rosanna Weksberg and Pasko Rakic and Zhandong Liu and Zoghbi, {Huda Y.}",
year = "2013",
month = "3",
day = "1",
doi = "10.1101/gad.207456.112",
language = "English",
volume = "27",
pages = "485--490",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "5",

}

TY - JOUR

T1 - Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p

AU - Han, Kihoon

AU - Gennarino, Vincenzo Alessandro

AU - Lee, Yoontae

AU - Pang, Kaifang

AU - Hashimoto-Torii, Kazue

AU - Choufani, Sanaa

AU - Raju, Chandrasekhar S.

AU - Oldham, Michael C.

AU - Weksberg, Rosanna

AU - Rakic, Pasko

AU - Liu, Zhandong

AU - Zoghbi, Huda Y.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.

AB - Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpGbinding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 39 untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 39 UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development.

KW - 3' UTR

KW - HDAC4

KW - Human fetal brain

KW - MeCP2

KW - miR-483-5p

KW - TBL1X

UR - http://www.scopus.com/inward/record.url?scp=84874895206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874895206&partnerID=8YFLogxK

U2 - 10.1101/gad.207456.112

DO - 10.1101/gad.207456.112

M3 - Article

C2 - 23431031

AN - SCOPUS:84874895206

VL - 27

SP - 485

EP - 490

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 5

ER -