lincRNA: A recently discovered RNA organizes stem cell differentiation

What makes a scientist’s heart go pitter-patter? Something like this:

When the Broad team discovered more than 3,500 unique lincRNAs in the human and mouse genomes in 2009, “the potential was enormous, and we wanted to know what they could be doing.”

[Source: Technology Review]

Here’s the scenario: A team of researchers at the Broad Institute (a joint operation of Harvard University and Massachusetts Institute of Technology, USA) discovered in 2009 that human and mouse genomes were encoded to produce thousands of a hitherto unknown form of RNA. The role of RNA, as commonly understood, is to carry the genetic code for protein production from the DNA to the locations of protein manufacture. Over the years, however, new forms of RNA were discovered – microRNA, mRNA, siRNA, RNAi, among others – and the range of function for RNA extended. In fact, the team at Broad Institute had discovered a form of RNA that didn’t appear to have any role in the coding and manufacturing of proteins. Called a lincRNA for ‘large intergenic non-coding RNA’, this form of RNA was found in all cells in great numbers. The team eventually identified over 3500 unique forms of lincRNAs. The question staring them in the face and making their adrenalin pump (so to speak) was, of course, what do all these lincRNAs do?

It turns out that at least one of the things lincRNAs do is coordinate and organize the assembly of proteins in embryonic stem cells – and probably all other cells as well. This is something of a revelation. It has always been thought that proteins themselves direct the development of cells, now it appears that lincRNAs provides the structure – a kind of chemical scaffold – on which cell protein is assembled. In stem cells, it is the role of lincRNAs to provide the all-important control of whether a stem cell remains pluripotent (able to turn into almost any other kind of cell) or differentiates into a specific type of adult cell. This role is so important to the development of life that discovery of a previously unknown agent of such influence as lincRNA is almost shocking. Except that for biochemists this is the kind of thing that makes a career, or even a Nobel.

The researchers at Broad Institute, with first author Mitchell Guttman and senior staffers David Root and Eric Lander, decided in 2009 to concentrate on the activity of lincRNA in embryonic stem cells, which are heavily studied and of such obvious biological importance. In order to determine the role of lincRNA, they used genetic techniques to turn off and on the production of specific lincRNAs. Eventually they isolated about 100 forms of lincRNA that appeared to be at work in stem cells. From there they used biochemical analysis to follow the effect of lincRNA on cell protein.

The results of their work, published in the journal Nature [28 August 2011, paywalled, lincRNAs act in the circuitry controlling pluripotency and differentiation] is the first comprehensive view of lincRNA at work in a specific cell type. As one of the researchers put it, “lincRNAs are like team captains, bringing together the right [protein] players to get a job done.”

Sports analogies aside, the discovery of a whole new class of RNA – one with such a powerful role in the development of cells – opens the way to explore yet another massive complication in the processes of life. This might be overstating the case, but probably not. In any case, this is the kind of challenge that scientists live for, which is definitely not an overstatement. The opportunity to experiment and provide answers to big questions (even if the subject matter is very small) is rare enough.

Research Spectrum

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