Abstract
Tandem repeats of various trinucleotide motifs are frequent entities in transcripts, and RNA structures formed by these sequences depend on the motif type and number of reiterations. The functions performed by normal triplet repeats in transcripts are poorly understood, but abnormally expanded repeats of certain types trigger pathogenesis in several human genetic disorders known as the triplet repeat expansion diseases (TREDs). The diseases caused by expanded non-coding CUG and CGG repeats in transcripts include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome. Another group of disorders in which transcripts containing translated CAG repeats play an auxiliary role in pathogenesis include Huntington’s disease and several spinocerebellar ataxias. In this review, we gathered existing knowledge regarding the structural features of triplet repeats in transcripts and discussed this in the context of various pathogenic mechanisms assigned to toxic RNA repeats. These mechanisms include aberrant alternative splicing, the inhibition of nuclear transport and export, induction of the innate immune response, alteration of a microRNA biogenesis pathway and abnormal activation of an RNA interference pathway. We also provide ideas for future investigations to reveal further mechanisms of pathogenesis directly triggered by mutant RNA repeats in TREDs.
About the authors
Paulina Galka-Marciniak graduated in medical biotechnology in 2010 at the Poznan University of Medical Sciences, Poland. She is currently working on her PhD investigating the genetic approaches to RNAi-based experimental therapy of Triplet Repeat Expansion Diseases, the nonspecific immunological side effects triggered by RNAi and microRNA reagents and the mechanisms of microRNA biogenesis.
Martyna Urbanek is a MSc student in medical biotechnology at Poznan University of Medical Science and BCS student in algorithmics and programming engineering at Adam Mickiewicz University. Her research interests span nonspecific immunological effects of RNA interference reagent, RNA visualization in live cells and broadly defined bioinformatics including microarray analysis.
Professor Wlodzimierz J. Krzyzosiak is Head of Laboratory of Molecular Biomedicine at the Institute of Bioorganic Chemistry, Polish Academy of Sciences in Poznan, Poland. He received his PhD degree from Adam Mickiewicz University in Poznan, and held fellowships at prestigious research centers in the UK, France, USA and Japan. Professor Krzyzosiak has a long-lasting interest in the biochemistry of RNA, and his research achievements include developing a method of RNA structure probing by metal ion-induced cleavages. He also has a long research record in studying the role of RNA repeats in molecular pathology of triplet repeat expansion diseases.
©2012 by Walter de Gruyter Berlin Boston
