Faghihi, M A et al ., 2010  reported that BACE1-antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed, miR-485-5p and BACE1-antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA (see the figure below)

Screenshot from 2013-06-20 01:08:56

In order to find confirm if the BACE1-AS competes with th microRNA, the group performed RT-PCR on the RNA samples from different tissues of human and mouse and found that the expression of BACE1, BACE1-AS and mir-485-5p was higher in brain than any other tissue. and since BACE1 gene is know to be involved in Alzheimer’s disease the group examined second set of RNA samples from control subjects and individuals with Alzheimer’s disease.

Initially, they examined the parietal lobe and cerebellum of 5 subjects with Alzheimer’s disease and 5 normal elderly individuals (20 samples total). BACE1-AS, and to a lesser degree BACE1, transcripts were up-regulated in Alzheimer’s disease patients compared to control individuals and miR-485-5p was down-regulated by 30% in parietal lobe and close to 60% in cerebellum of Alzheimer’s disease patients

Screenshot from 2013-06-20 07:44:31

Later they also examined a second set of RNA samples from 35 Alzheimer’s disease and 35 control individuals since samples were not available for all regions, they examined for only few regions and found consistent results as there previous works.

BACE1-AS transcript concentrations were up-regulated in all four regions tested. To a lesser degree, BACE1 transcripts were up-regulated in entorhinal cortex as well as in superior frontal gyrus. On the other hand, miR-485-5p was significantly reduced in entorhinal cortex and hippocampus. However, miR-485-5p was not significantly altered in cerebellum and superior frontal gyrus. The difference between miR-485-5p expressions in cerebellum of the two sets of RNA samples can conceivably be explained by the relatively high variability among human samples. (see the figure below)

Screenshot from 2013-06-20 07:53:32

They conclude demonstrating the potential competition between microRNA and antisence lncRNA for a binding site in the sixth exon of BACE1 gene and hence regulating its level. This study uncovers yet another post-transcriptional mode of gene regulation in which lncRNAs are involved.

Later in 2012 Keniry et al., demonstrated similar post-transcriptional regulation by another lncRNA (h19 lincRNA)  which included miR-675.

Advertisements