Dysregulation of two novel lncRNAs in heritable conditions.
(A) Placental trophoblasts normally invade the uterine wall as the placenta remodels
the maternal vasculature. van Dijk et al. propose that a lncRNA transcribed from the
HELLP locus regulates the transition from proliferation to invasion of trophoblasts (3).
(B) Mutations predisposed to HELLP are present in fetal tissue and appear to promote
increased expression of the HELLP lncRNA (pink) in placental trophoblasts, promoting
trophoblast proliferation at the expense of differentiation and invasion.
(C) The CISTR-ACT locus (purple) and DA125942, a lncRNA transcribed from the
CISTR-ACT locus, interact in cis with PTHLH and in trans with SOX9. Maass et al.
conclude that DA125942 organizes chromatin to coordinate transcription
of multiple loci involved in cartilage differentiation (4).
(D) A chromosomal translocation found in BDE patients disrupts the ability of
DA125942 to bind the PTHLH locus in cis, potentially causing premature
chondrocyte differentiation at the expense of proliferation and bone elongation.
L-INC-ing Noncoding RNAs to Human Disease
The list of functions of long noncoding RNAs (lncRNAs) in human tissues is rapidly growing. To underscore their critical role in human health, two reports associate altered expression of lncRNAs with the heritable syndromes HELLP and brachydactyly type E
LncRNAs (pronounced "link") are long non-coding RNAs that are emerging as important regulators of gene expression in biological processes and diseases.
Listed below in the current issue of the Journal of Clinical Investigation, are two papers connecting lncRNAs to inherited conditions in humans.
A misplaced lncRNA causes brachydactyly in humans by Sylvia Bähring and colleagues at the Experimental and Clinical Research Center in Berlin, found a chromosomal translocation that disrupts the expression of a lncRNA. This disruption alters the expression of the genes PTHLH and SOX9 and results in brachydactyly, an inherited malformation of the fingers and toes.
The HELLP syndrome, which is a group of symptoms occurring in pregnant women that leads to pre-term delivery, was also found to be caused by a lncRNA. Researchers led by Cees Oudejans at the VU University Medical Center in Amsterdam identified a lncRNA on chromosome 12 that activated a set of genes which control the development of the placenta. HELLP-babies link a novel lincRNA to the trophoblast cell cycle
In a companion commentary, Norman Sharpless of the University of North Carolina at Chapel Hill provides an overview of lncRNA biology and discusses the role of lncRNAs in heritable human diseases. Genetic "lnc"-age of Non-Coding RNAs to Human Disease
Original article: http://www.eurekalert.org/pub_releases/2012-10/joci-tm101712.php