MeCP2 Suppresses Nuclear MicroRNA Processing and Dendritic Growth by Regulating the DGCR8 Drosha Complex.(Dev Cell. 2014 Mar 10;28(5):547-60. doi: 10.1016/j.devcel.2014.01.032.)

報告日期: 2014/10/31
報告時間: 5:10/6:00
報告學生: 李婕寧
講評老師: 陳玉玲
附件下載: 下載[1425-1412163709-1.pdf] 

MeCP2 Suppresses Nuclear MicroRNA Processing and Dendritic Growth by Regulating the DGCR8/Drosha Complex

 

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

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

 

Student: Jie-Ning Li (李婕寧)       Time: 2014/10/31 17:10-18:00

Commentator: Dr. Chen, Yuh-Ling     Place: Room602

 

Abstract

 

MeCP2 is a methyl-CpG binding protein which functions as a transcriptional repressor by recruiting histone deacetylase complex (HDAC). MeCP2 has been known to play an important role in regulating gene expression transcriptionally. Loss- and gain- of-function mutations in MECP2 gene cause Rett syndrome (RTT) and autism, respectively. Therefore, the amount of MeCP2 protein is critical for central system neuron (CNS) development and function. MicroRNAs (miRNAs) are a group of non-coding RNAs which regulate messenger RNAs in the posttranscriptional level through targeting their 3'-untranslated region (3'UTR). Primary miRNAs (pri-miRNAs) are initially cleaved to premature miRNAs (pre-miRNAs) by Drosha, a RNaseenzyme in the nucleus with its cofactor DiGeorge syndrome critical region 8 (DGCR8). These pre-miRNAs are then transported to cytoplasm and cleaved by Dicer, becoming mature miRNA duplex. It has been reported that gene expression profile is altered in the brain of mecp2 null mice indicating that MeCP2 has the positive role in gene expression or controlling the posttranscriptional repressors like microRNAs. The authors find that phosphorylated MeCP2 at Serine 80 bind directly to DGCR8 and suppress the microRNA biogenesis by interfering Drosha/DGCR8 complex formation. Proteins including CREB and LIMK1 targeted by MeCP2-suppressed microRNAs are enhanced by gain of function of MeCP2 and lead to inhibition of dendritic and spine growth.

 

 

References:

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