Attenuation of gene expression by a trinucleotide repeat-rich tract from the terminal exon of the rat hepatic polymeric immunoglobulin receptor gene

A 359 bp terminal exon fragment of the rat polymeric immunoglobulin receptor gene has been tested for biological effects. The fragment contains an S1 nuclease-sensitive microsatellite with d(GGA) and d(GAA) trinucleotide repeats that are expressed discordantly in the 3′UTRs of liver mRNAs encoded by the single copy gene. When human A293 cells are transfected with expression plasmids carrying this fragment in forward orientations, flanking or replacing poly(A) cassettes in the 3′ ends of the transcription units, luciferase reporter gene expression is attenuated 47 to 59% or 98.5%, respectively. In contrast, when the fragment is tested similarly in reverse orientation, there is significantly less or no attenuation of gene expression. These observations, and computer models of partial triplet repeat DNA tertiary and RNA secondary structures, suggest that this fragment might regulate gene expression by orientation and position-dependent mechanisms at transcriptional and post-transcriptional levels.