What Do You Do, lincRNA? 09/14/2011
Michelle Bialeck
In two recently published studies, researchers from the Broad Institute of the Massachusetts Institute of Technology and Harvard University have begun to describe the role of non-coding RNAs within the cell. These studies are changing the way biologists understand the regulation of gene expression in embryonic development and disease.
In the first paper, published Nature, Mitchell Guttman and his Broad colleagues propose a model for lincRNA function in which lincRNAs and regulatory proteins link together to create cell-type-specific RNA-protein complexes. Source: Nature.
In the first paper, published in Nature, Mitchell Guttman and his Broad colleagues performed a loss-of-function RNAi study on large intergenic non-coding RNAs (lincRNAs) expressed in embryonic stem cells to understand their function within the cells (1). Through this experiment, they found that the knockdown of some lincRNAs affected gene expression within the cell and subsequently the pluripotency and development of the stem cell.
Furthermore, the researchers propose a model for lincRNA function in the cell based on their experimental data. In this model, specific transcription factors regulate expression of lincRNAs, and these lincRNAs link other regulatory proteins to create cell-type-specific RNA-protein complexes.
To describe lincRNAs role in embryonic development, Guttman uses the analogy of a battle between proteins that maintain pluripotency and other proteins that promote differentiation. “Proteins can be thought of as the soldiers in this battle. They’ll do their job, but they need something to coordinate their actions,” says Guttman. “The lincRNAs can be thought of as the sergeants, the group leaders, who take these different proteins and coordinate them into a coherent response.”
In a second paper, published in Genes and Development, John Rinn and his Broad colleagues catalogued more than 8000 human lincRNAs (2). To create this catalog, Rinn’s team combined existing lincRNA annotations with RNA-seq data they collected from 24 tissues and cell types. For each lincRNA, the catalog provides the more than 30 properties, including sequence, structure, and protein associations.
“Somebody does not have to be a computational biologist with massively parallel new sequencing tools,” said Rinn. “They now have an Excel file that they can sort columns by and find lincRNAs that might be involved in their disease, so really we’ve handed it over to the community in a really user-friendly map.”
Analyzing the catalog, the Broad team found that lincRNAs are very tissue-specific, much more specific than protein coding genes. Because of this high specificity, lincRNAs make excellent descriptors of different subpopulations of cells, including diseased cells for diagnostic purposes.
Currently, Guttman, Rinn, and their Broad colleagues are continuing to investigate the role of non-coding RNA in embryonic development as well as in normal and diseased cells. By understanding this role, these researchers hope to engineer or manipulate specific lincRNAs to treat disease.
“Imagine you’re studying hematopoiesis, or you’re studying fat development, or you’re studying cancer, all of this, lincRNAs will almost certainly play a role in all of these processes. But we’ve been kind of missing it until now,” said Guttman.
References
- Guttman, M., J. Donaghey, B.W. Carey, M. Garber, J.K. Grenier, G. Munson, G. Young, A.B. Lucas, et al. 2011. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011 Aug 28. doi: 10.1038/nature10398. [Epub ahead of print]
- Cabili, M.N., C. Trapnell, L. Goff, M. Koziol, B. Tazon-Vega, A. Regev, and J.L. Rinn. 2011. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011 Sep 2. [Epub ahead of print]