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Where does each class of RNA reside in the cell? The spatial arrangement of RNAs is an interesting question that necessitates an improved understanding of the proteins bound to RNAs – as showcased in this month’s RBPome issue of Genome Biology. In the issue, Edwin Cuppen and colleagues from the University Medical Center Utrecht, the Netherlands, perform a transcriptome-wide survey of RNA localization, only to arrive at some surprising findings about one specific class: long non-coding RNAs (lncRNAs).

The functions of lncRNAs, and indeed whether most of them even have a function, have remained something of a mystery, although one which is gradually being solved in a piecemeal fashion. With each characterization of a lncRNA, we wonder whether the reported function might represent a new paradigm, defining a whole class of non-coding transcripts.

There are two proposed features of lncRNAs that until recently seemed like good bets:

1) they mostly localize to the nucleus, as most lncRNA functions that we know of relate to regulating the genome
2) they don’t associate with ribosomes, because they are not coding transcripts and so have no purpose in interacting with the translational machinery

However, recent work has suggested that some bona fide lncRNAs – that is, RNAs whose untranslated status can be validated – associate with ribosomes. In a study that separated cells into nuclear, cytosolic and ribosomal fractions, Cuppen and colleagues take this principle one step further, with their finding that a very large number of lncRNAs are associated with ribosomes.

Perhaps even more surprisingly, according to the fractionation experiment, only a minority of lncRNAs are to be found in the nucleus, which puts a dent in the idea that the function of most lncRNAs is to regulate the genome.

So why are so many lncRNAs let loose outside the nucleus? Cuppen and colleagues speculate that these lncRNAs may regulate ribosomal complexes in some fashion – perhaps even in a way that maintains the idea of genome regulation, but further downstream, at the translational step.


Written by Naomi Attar (@naomiattar), Senior Editor for Genome Biology.



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Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes

van Heesch S, van Iterson M, Jacobi J, Boymans S, Essers PB, de Bruijn E, Hao W, MacInnes AW et al.

Genome Biology 2014, 15:R6

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