Xist

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Xist is a non-coding RNA (ncRNA) which is encoded for on X chromosomes[1]. The ncRNA is responsible for the inactivation of X chromosomes in embryos to ensure that only one X chromosome is active after the first few days of embryonic development - inactivation is random resulting in a combination of paternal and maternal X chromosomes being active. This is sometimes referred to as dosage compensation and will always result in just one X chromosome being active, even when non-disjunction results in the incorrect number of X chromosomes being present in the developing embryo[2]. The inactivated chromosomes become densely packed forms of heterochromatin, structures which are known as a Barr bodies[3].

Mechanism of Action

Xist originates from an area on the X chromosome known as the X inactivation centre. Following transcription, Xist moves along the X chromosome covering the majority of the genetic material - roughly 15% of genes at the end of the X chromosomes evade inactivation[4]. Exactly how this occurs, and how the cell decides which chromosome to inactivate is still unknown[5].

However, research has suggested that the mechanism by which inactivation occurs must be found within Xist since when this section of DNA was transferred to another autosome, the autosome was inactivated in the same way that a human X chromosome is[6].

Xist also works alongside another ncRNA known as Tsix which is encoded for in the same section of DNA as Xist is, just on the opposite strand. Tsix and Xist cannot both be expressed at the same time and therefore, Tsix can only be expressed on active X chromosomes. Research in this area may explain the exact method by which X inactivation occurs[7].

Disease

Mutations in Xist can result in a phenomenon known as skewed X-inactivation which occurs when the inactivation of either maternal or paternal chromosome is favoured and this can result in a greater pre-disposition to some diseases[8].

Refrerences

  1. Elliott D, Ladomery M. Molecular biology of RNA. Oxford: Oxford University Press; 2011.
  2. Brown C, Ballabio A, Rupert J, Lafreniere R, Grompe M, Tonlorenzi R et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349(6304):38-44.
  3. Elliott D, Ladomery M. Molecular biology of RNA. Oxford: Oxford University Press; 2011.
  4. Carey N. Junk DNA. London: Icon; 2015.
  5. Carey N. Junk DNA. London: Icon; 2015.
  6. Lee J, Strauss W, Dausman J, Jaenisch R. A 450 kb Transgene Displays Properties of the Mammalian X-Inactivation Center. Cell. 1996;86(1):83-94.
  7. Carey N. Junk DNA. London: Icon; 2015.
  8. Minks J, Robinson W, Brown C. A skewed view of X chromosome inactivation. Journal of Clinical Investigation. 2008;118(1):20-23.
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