title: Involvement of FMRP in Primary MicroRNA Processing via Enhancing Drosha Translation.
abstract: Fragile X mental retardation protein (FMRP), associated with fragile X syndrome, is known as an RNA-binding protein to regulate gene expression at post-transcriptional level in the brain. FMRP is also involved in microRNA (miRNA) biogenesis during the process of precursor miRNA (pre-miRNA) into mature miRNA. However, there is no description of the effect of FMRP on primary miRNA (pri-miRNA) processing. Here, we uncover a novel role of FMRP in pri-miRNA processing via controlling Drosha translation. We show that the expression of DROSHA protein, instead of its messenger RNA (mRNA) transcripts, is downregulated in both the hippocampus of Fmr1-knockout mice and the FMRP-knockdown Neuro-2a cells. Overexpression or knockdown FMRP does not alter Drosha mRNA stability. Immunoprecipitation and polysome analyses demonstrate that FMRP binds to the Drosha mRNA and enhances its translation. Additionally, we show that loss of FMRP in Fmr1-deficient mice results in the accumulation of three in six analyzed pri-miRNAs and the reduction of the corresponding pre-miRNAs and mature miRNAs. Thus, our data suggest that FMRP is involved in pri-miRNA processing via enhancing DROSHA expression that may play an important role in fragile X syndrome.
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.|Department of Children's Rehabilitation, Foshan Maternity and Child Healthcare Hospital Affiliated to Southern Medical University, Foshan, China.
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Wan
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Hai-Xuan
authors.initials: HX
authors.lastname: Yang
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Yong-Ting
authors.initials: YT
authors.lastname: Zhou
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Ye
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: Zhao
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Gao
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liao
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China. yyh168@sina.com.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Yi
authors.affiliation: Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, 250 Changang East Road, Guangzhou, 510260, China. longyuesheng@gzhmu.edu.cn.
authors.forename: Yue-Sheng
authors.initials: YS
authors.lastname: Long
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs; D012333:RNA, Messenger; D043244:Ribonuclease III; C497684:Fmr1 protein, mouse; C513400:Drosha protein, mouse
keywords: DROSHA; FMRP; Fragile X syndrome; MicroRNA; Translation regulation