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Discovery of Gene Silencing Site

A team of IIGB scientists led by geneticist Xuemei Chen have conducted a study on plants (Arabidopsis) showing that the site of repression of target gene expression occurs on the endoplasmic reticulum (ER), a cellular organelle that is an interconnected network of membranes. Study results appear in the journal Cell.

RNA molecules, made from DNA, are best known for their role in protein production. MicroRNAs (miRNAs), however, are short (~22) nucleotide RNA sequences found in plants and animals that do not encode proteins but act in gene regulation and, in the process, impact almost all biological processes — from development to physiology to stress response.

Present in almost in every cell, microRNAs are known to target tens to hundreds of genes each and to be able to repress, or “silence,” their expression.  What is less well understood is how exactly miRNAs repress target gene expression.

“Our study is the first to demonstrate that the ER is where miRNA-mediated translation repression occurs,” said lead researcher Xuemei Chen, a professor of plant cell and molecular biology and a Howard Hughes Medical Institute-Gordon and Betty Moore Foundation Investigator. “To understand how microRNAs repress target gene expression, we first need to know where microRNAs act in the cell.  Until now no one knew that membranes are essential for microRNA activity.”

Next, her lab will attempt to crack the mechanism of miRNA-mediated translational inhibition. They will investigate, too, how miRNAs are recruited to the ER.

Research on miRNAs has increased tremendously since they were first identified about 20 years ago. In the case of diseases, if some genes are up- or down-regulated, miRNAs can be used to change the expression of these genes to fight the diseases, thus showing therapeutic potential.

Chen was joined in the study by Shengben Li (first author of the research paper), Lin Liu, Xigang Liu, Yu Yu, Lijuan Ji and Natasha Raikhel at UC Riverside; Xiaohong Zhuang and Liwen Jiang at the Chinese University of Hong Kong; Xia Cui and Xiaofeng Cao at the Chinese Avademy of Sciences, Beijing; Zhiqiang Pan at the University of Mississippi; Beixin Mo at Shenzhen University, China; and Fuchun Zhang at Xinjiang University, China.

The study was supported by grants to Chen from the National Institutes of Health, the National Science Foundation, and the Howard Hughes Medical Institute and Gordon and Betty Moore Foundation.

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