Probing genomic dark matter

In an editorial on the debate surrounding the role and abundance of “dark matter” RNA, BMC Biology concluded that we need to know more about the function of specific non-coding RNAs before we can make more general judgments about their role.

So what do we know about ncRNA function so far? Quite a lot – but only about a few of them. Known functional ncRNAs, and the diversity of methods by which they might act, are well-covered by Chris Ponting in a 2009 review. But those dark matter RNAs for which we have a known function and mechanism are hugely outnumbered by those for which we don’t, with less than 100 being well-characterized so far. There are significantly more for which intriguing correlations have been seen – between long ncRNAs and certain cancers, for example (collated in a recent Molecular Cancer review) – but correlation does not equal causation, of course, and for many of these a definitive function or proposed mechanism are missing.

A recent study in malaria discussed this month in BMC Biology provides a tantalizing example. The authors detected long ncRNAs which are present in the pathogenic human blood stage, and further investigation showed that these have some sequence similarity to promoters of the var genes – these encode a family of virulence factors which regularly switch expression to avoid the human immune response, and whose regulation is currently mysterious. But while this is a suggestive and interesting observation, we don’t know anything about the mechanism by which these ncRNAs might act – although this has not inhibited speculation in the article itself and the accompanying BMC Biology commentary. The challenge now will be to turn genomic observations into biochemical insights.

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