Implications of X-linked gene regulation for sex differences in disease pathogenesis (comment on DOI 10.1002/bies.201100047).Comments Comment on: Bioessays. 2011 Nov;33(11):791-802; PMID: 21953569

摘要

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a post-transcriptional level and play a critical role in maintaining immunological homeostasis. Dysregulation of miRNA expression may underlie development of immune-mediated diseases, ranging from cancers to autoimmune diseases [1]. The hypothesis put forth by Pinheiro et al. [1] is that because a disproportionately high number of miRNAs are located on the X chromosome, as compared with the autosomes, these X-linked miRNAs may contribute to sex differences in disease pathogenesis. The authors document X-linked miRNAs in humans and mice that have associated immune function and speculate that if miRNAs escape X chromosome inactivation, this could result in differential gene expression and regulation between males and females. Although it has not been demonstrated that X-linked miRNAs escape X chromosome inactivation, the authors provide comparative and molecular evidence to support the hypothesis that sex chromosome- linked miRNAs are conserved across species and play fundamental roles in regulating immunity and disease pathogenesis. Whether miRNAs are determinants of sex differences in the outcome of disease remains to be shown.