title: Regulation of mRNA Translation by MID1: A Common Mechanism of Expanded CAG Repeat RNAs.
abstract: Expansion of CAG repeats, which code for the disease-causing polyglutamine protein, is a common feature in polyglutamine diseases. RNA-mediated mechanisms that contribute to neuropathology in polyglutamine diseases are important. RNA-toxicity describes a phenomenon by which the mutant CAG repeat RNA recruits RNA-binding proteins, thereby leading to aberrant function. For example the MID1 protein binds to mutanthuntingtin(HTT) RNA, which is linked to Huntington's disease (HD), at its CAG repeat region and induces protein synthesis of mutant protein. But is this mechanism specific to HD or is it a common mechanism in CAG repeat expansion disorders? To answer this question, we have analyzed the interaction between MID1 and three other CAG repeat mRNAs,Ataxin2(ATXN2),Ataxin3(ATXN3), andAtaxin7(ATXN7), that all differ in the sequence flanking the CAG repeat. We show thatATXN2, ATXN3, andATXN7bind to MID1 in a CAG repeat length-dependent manner. Furthermore, we show that functionally, in line with what we have previously observed for HTT, the binding of MID1 toATXN2, ATXN3, andATXN7mRNA induces protein synthesis in a repeat length-dependent manner. Our data suggest that regulation of protein translation by the MID1 complex is a common mechanism for CAG repeat containing mRNAs.
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Nadine
authors: N
authors: Griesche
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Judith
authors: J
authors: Schilling
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Stephanie
authors: S
authors: Weber
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Marlena
authors: M
authors: Rohm
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Verena
authors: V
authors: Pesch
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Frank
authors: F
authors: Matthes
authors: Experimental Neurology, Goethe University Medical School Frankfurt, Germany.
authors: Georg
authors: G
authors: Auburger
authors: German Center for Neurodegenerative Diseases Bonn, Germany.
authors: Sybille
authors: S
authors: Krauss
keywords: CAG repeat expansion; MID1; RNA-binding proteins; RNA-toxicity; polyglutamine diseases