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MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex.

May 17, 2014 - 6:21am
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MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex.

Dev Cell. 2014 Mar 10;28(5):547-60

Authors: Cheng TL, Wang Z, Liao Q, Zhu Y, Zhou WH, Xu W, Qiu Z

Abstract
Loss- and gain-of-function mutations of the X-linked gene MECP2 (methyl-CpG binding protein 2) lead to severe neurodevelopmental disorders in humans, such as Rett syndrome (RTT) and autism. MeCP2 is previously known as a transcriptional repressor by binding to methylated DNA and recruiting histone deacetylase complex (HDAC). Here, we report that MeCP2 regulates gene expression posttranscriptionally by suppressing nuclear microRNA processing. We found that MeCP2 binds directly to DiGeorge syndrome critical region 8 (DGCR8), a critical component of the nuclear microRNA-processing machinery, and interferes with the assembly of Drosha and DGCR8 complex. Protein targets of MeCP2-suppressed microRNAs include CREB, LIMK1, and Pumilio2, which play critical roles in neural development. Gain of function of MeCP2 strongly inhibits dendritic and spine growth, which depends on the interaction of MeCP2 and DGCR8. Thus, control of microRNA processing via direct interaction with DGCR8 represents a mechanism for MeCP2 regulation of gene expression and neural development.

PMID: 24636259 [PubMed - indexed for MEDLINE]

MeCP2 caught moonlighting as a suppressor of MicroRNA processing.

May 17, 2014 - 6:21am
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MeCP2 caught moonlighting as a suppressor of MicroRNA processing.

Dev Cell. 2014 Mar 10;28(5):477-8

Authors: Woo JS, Kim VN

Abstract
MeCP2 is a transcriptional regulator important for neurodevelopment and is involved in Rett syndrome and autism. In this issue of Developmental Cell, Cheng and colleagues (2014) report that MeCP2 also regulates microRNA biogenesis. MeCP2 phosphorylation induces a direct interaction with DGCR8, leading to reduced microRNA processing and retardation of dendritic growth.

PMID: 24636253 [PubMed - indexed for MEDLINE]

Interstitial 12p13.1 deletion involving GRIN2B in three patients with intellectual disability.

May 16, 2014 - 9:05am
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Interstitial 12p13.1 deletion involving GRIN2B in three patients with intellectual disability.

Am J Med Genet A. 2013 Oct;161(10):2564-9

Authors: Dimassi S, Andrieux J, Labalme A, Lesca G, Cordier MP, Boute O, Neut D, Edery P, Sanlaville D, Schluth-Bolard C

Abstract
We report on three patients presenting moderate intellectual disability, delayed language acquisition, and mild facial dysmorphia. Array-CGH studies revealed overlapping interstitial 12p13.1 microdeletions encompassing all or part of GRIN2B. GRIN2B encodes the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor. This receptor is a heteromeric glutamate-activated ion channel, present throughout the central nervous system. It plays a critical role in corticogenesis, neuronal migration, and synaptogenesis during brain development. GRIN2B alterations, including mutation and gene disruption by apparently balanced chromosomal rearrangements, have been described in patients with intellectual disability and autism spectrum disorder. We report here on the first cases of GRIN2B deletion, enlarging the spectrum of GRIN2B abnormalities. Our findings confirm the involvement of this gene in neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.

PMID: 23918416 [PubMed - indexed for MEDLINE]

Sexual experience increases oxytocin receptor gene expression and protein in the medial preoptic area of the male rat.

May 16, 2014 - 9:05am
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Sexual experience increases oxytocin receptor gene expression and protein in the medial preoptic area of the male rat.

Psychoneuroendocrinology. 2013 Sep;38(9):1688-97

Authors: Gil M, Bhatt R, Picotte KB, Hull EM

Abstract
Oxytocin (OT) promotes social and reproductive behaviors in mammals, and OT deficits may be linked to disordered social behaviors like autism and severe anxiety. Male rat sexual behavior is an excellent model for OT regulation of behavior, as its pattern and neural substrates are well characterized. We previously reported that OT microinjected into the medial preoptic area (MPOA), a major integrative site for male sexual behavior, facilitates copulation in sexually experienced male rats, whereas intra-MPOA injection of an OT antagonist (OTA) inhibits copulation. In the present studies, copulation on the day of sacrifice stimulated OTR mRNA expression in the MPOA, irrespective of previous sexual experience, with the highest levels observed in first-time copulators. In addition, sexually experienced males had higher levels of OTR protein in the MPOA than sexually naïve males and first-time copulators. Finally, intra-MPOA injection of OT facilitated mating in sexually naive males. Others have reported a positive correlation between OT mRNA levels and male sexual behavior. Our studies show that OT in the MPOA facilitates mating in both sexually naive and experienced males, some of the behavioral effects of OT are mediated by the OTR, and sexual experience is associated with increased OTR expression in the MPOA. Taken together, these data suggest a reciprocal interaction between central OT and behavior, in which OT facilitates copulation and copulation stimulates the OT/OTR system in the brain.

PMID: 23474276 [PubMed - indexed for MEDLINE]

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