Long non-coding RNAs (lncRNAs) are RNA molecules of more than two hundred nucleotides in length, derived from non-coding regions of the genome. Although lncRNA does not encode any protein, their expression in different tissues and developmental stages remains specific, indicating that lncRNA has important biological significance.
Thousands of lncRNAs have been discovered with the help of sequencing technology, but the biological functions of these lncRNAs remain a mystery. Researchers at the Second Military Medical University published an article in Nature Communications, revealing a molecular mechanism by which lncRNA controls human embryonic stem cell (hESC) self-renewal. The author of the article is Professor Houqi Liu and Yue Wang of the Second Military Medical University.
Growth arrest specific transcript 5 (GAS5) is a lncRNA associated with growth arrest and is also known as a tumor suppressor. The researchers found that GAS5 is expressed at high levels in hESC and is directly regulated by the pluripotency factors OCT4 and SOX2. Studies have shown that GAS5 knockdown can seriously damage the self-renewal of hESC, and overexpression can significantly promote hESC self-renewal. Further studies have shown that GAS5 protects NODAL from degradation, thereby maintaining NODAL signaling.
Studies have shown that the above pluripotency factors, GAS5 and NODAL form a feedforward signal loop that maintains hESC self-renewal. Given the stem cell specificity of this regulatory function of GAS5, the researchers suggest that the function of lncRNA may be different in different cell types.
It has been found that some lncRNAs recruit regulatory complexes through RNA-protein interactions, which in turn affects the expression of nearby genes. It may be for this reason that lncRNA expression is often associated with expression of nearby genes. However, this association analysis is not easy. Scientists at the Broad Institute have recently achieved important results in this area. Their published article in Nature reveals the local regulation of lncRNA on gene expression.
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