Abstract
Xist, the master regulator of the X chromosome inactivation in mammals, is a 17 kb lncRNA that acts in cis to silence the majority of genes along the chromosome from which it is transcribed. The two key processes required for Xist RNA function, localisation in cis and recruitment of silencing factors, are genetically separable, at least in part. Recent studies have identified Xist RNA sequences and associated RNA-binding proteins (RBPs) that are important for these processes. Notably, several of the key Xist RNA elements correspond to local tandem repeats. In this review, I use examples to illustrate different modes whereby tandem repeat amplification has been exploited to allow orthodox RBPs to confer new functions for Xist-mediated chromosome inactivation. I further discuss the potential generality of tandem repeat expansion in the evolution of functional long non-coding RNAs (lncRNAs).
Highlights
The long non-coding RNA Xist mediates X chromosome inactivation (X inactivation), the process that, in mammals, equalises levels of X-linked gene expression in XX female relative to XY male cells [1,2,3,4,5]
One possibility is that an RNA-binding proteins (RBPs) that binds to a single site in the prototypic Xist long non-coding RNAs (lncRNAs) may have a previously evolved interaction with a known transcriptional repressor
The expansion of local tandem repeats during the evolution of Xist RNA provides an instructive example of how lncRNAs may become functionalised through natural selection
Summary
The long non-coding RNA (lncRNA) Xist mediates X chromosome inactivation (X inactivation), the process that, in mammals, equalises levels of X-linked gene expression in XX female relative to XY male cells [1,2,3,4,5]. Localised Xist RNA induces chromosome inactivation by recruiting factors that modify underlying chromatin and repress gene activity [7]. Further studies on Xist RBPs and the elements to which they bind have provided important advances in our understanding of Xist RNA localisation and Xist-mediated silencing. Analysis by 3D-SIM, a method for super-resolution light microscopy, has revealed that Xist RNA colocalises with hnRNPU and Ciz within channel networks that pervade interphase chromosome territories, Non-coding RNA 2018, 4, 28; doi:10.3390/ncrna4040028 www.mdpi.com/journal/ncrna. Arrows indicate the activity of the silencing factors mediated chromatin silencing (red triangles). The sequence analysis of Xist RNA in mouse, human and other species has revealed that a significant proportion of the primary RNA sequence is comprised of blocks of local tandemly repeated elements, designated repeats A–F (Figure 2). For these findings in understanding the evolution of functional lncRNAs
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