title: Partners in crime: bidirectional transcription in unstable microsatellite disease.
abstract: Nearly two decades have passed since the discovery that the expansion of microsatellite trinucleotide repeats is responsible for a prominent class of neurological disorders, including Huntington disease and fragile X syndrome. These hereditary diseases are characterized by genetic anticipation or the intergenerational increase in disease severity accompanied by a decrease in age-of-onset. The revelation that the variable expansion of simple sequence repeats accounted for anticipation spawned a number of pathogenesis models and a flurry of studies designed to reveal the molecular events affected by these expansions. This work led to our current understanding that expansions in protein-coding regions result in extended homopolymeric amino acid tracts, often polyglutamine or polyQ, and deleterious protein gain-of-function effects. In contrast, expansions in noncoding regions cause RNA-mediated toxicity. However, the realization that the transcriptome is considerably more complex than previously imagined, as well as the emerging regulatory importance of antisense RNAs, has blurred this distinction. In this review, we summarize evidence for bidirectional transcription of microsatellite disease genes and discuss recent suggestions that some repeat expansions produce variable levels of both toxic RNAs and proteins that influence cell viability, disease penetrance and pathological severity.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Batra
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Charizanis
authors.forename: Maurice S
authors.initials: MS
authors.lastname: Swanson
mesh_terms: D004276:DNA, Satellite / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004276:DNA, Satellite