Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome
Joint Authors
Kelley, Karen
Chang, Shin-Ju E.
Lin, Shi-Lung
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-20
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats.
Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs) such as fragile X syndrome (FXS).
After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA)-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs.
However, the function of these repeat-associated miRNAs (ramRNAs) is unclear.
To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function.
Our studies showed that ramRNA-induced DNA methylation of the FMR1 5′-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP.
FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR)-activated long-term depression (LTD), leading to abnormal neuronal responses in FXS.
Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention.
American Psychological Association (APA)
Kelley, Karen& Chang, Shin-Ju E.& Lin, Shi-Lung. 2012. Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome. Neural Plasticity،Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-1002330
Modern Language Association (MLA)
Kelley, Karen…[et al.]. Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome. Neural Plasticity No. 2012 (2012), pp.1-10.
https://search.emarefa.net/detail/BIM-1002330
American Medical Association (AMA)
Kelley, Karen& Chang, Shin-Ju E.& Lin, Shi-Lung. Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome. Neural Plasticity. 2012. Vol. 2012, no. 2012, pp.1-10.
https://search.emarefa.net/detail/BIM-1002330
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1002330