Missing lincs guilty by association

US researchers have found evidence for over one thousand highly conserved long non-coding RNAs that they believe play functional roles in mammals.

Traditionally considered transcriptional noise, a small number of these long intervening non-coding RNAs (lincRNAs) have been shown to have certain functions. About ten have been described so far, by the same Broad Institute team behind the new study.

One example is Hotair, which the researchers say is involved in repressing gene expression, and another is Xist, which has a role in X-chromosome inactivation.

Using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq), the researchers mapped about 1600 lincRNAs, which they say have roles in different mammalian processes, from embryonic stem cell pluripotency to cell proliferation.

Their paper is published online in advance of publication in Nature.

They tracked the lincs down by mapping their distinctive chromatin signature against the “dark matter of the genome”, the vast spaces in between normal genes.

Interestingly, the majority of these lincRNAs sit next to transcription factors on the genome. The researchers speculate that many lincRNAs are involved in transcriptional control, perhaps in concert with the transcription factors.

To uncover their purpose, the researchers used a method they call “guilt by association”, pinpointing probable function by the function of the genes they are situated near.

The proof will be in the pudding. The team is planning RNAi studies to knock out the lincs and to observe the effects.