Non-coding RNA function

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The genetic determination of sex in humans, as in most mammals, is based on the presence of a pair of so-called sex chromosomes termed the X- and Y-chromosome. In addition to 23 pairs of somatic chromosomes, males carry one X- and one Y-chromosome, while females have two X chromosomes. To avoid a situation, in which female cells express twice the amount of gene products encoded on the X-chromosome compared to male cells, a process known as dosage compensation corrects the imbalance. In humans, dosage compensation is achieved by almost complete silencing of one of the X-chromosomes in female cells. The silenced X-chromosome condenses into a highly compact structure in the cell nucleus and most of the genes on the chromosome are not expressed. Initiation of X-chromosome silencing correlates with expression of the Xist gene locus. The Xi-specific transcript of this locus (Xist) is transcribed exclusively on the inactive copy of the X-chromosome. The Xist RNA does not contain genomic instructions for protein production, as do most RNA molecules. Instead Xist appears to function by interacting with the inactive X chromosome, in fact it is required for initiation of the dosage compensation process. This project will attempt to characterize Xist RNA interaction sites on the inactive X chromosome in female cells.

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