Control of mRNA stability contributes to low levels of nuclear polyA binding protein 1 PABPN1 in skeletal muscleReport as inadecuate

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Skeletal Muscle

, 3:23

First Online: 01 October 2013Received: 30 May 2013Accepted: 28 August 2013


BackgroundThe nuclear polyA binding protein 1 PABPN1 is a ubiquitously expressed proteinthat plays critical roles at multiple steps in post-transcriptional regulation ofgene expression. Short expansions of the polyalanine tract in the N-terminus ofPABPN1 lead to oculopharyngeal muscular dystrophy OPMD, which is an adult onsetdisease characterized by eyelid drooping, difficulty in swallowing, and weaknessin the proximal limb muscles. Why alanine-expanded PABPN1 leads to muscle-specificpathology is unknown. Given the general function of PABPN1 in RNA metabolism,intrinsic characteristics of skeletal muscle may make this tissue susceptible tothe effects of mutant PABPN1.

MethodsTo begin to understand the muscle specificity of OPMD, we investigated thesteady-state levels of PABPN1 in different tissues of humans and mice.Additionally, we analyzed the levels of PABPN1 during muscle regeneration afterinjury in mice. Furthermore, we assessed the dynamics of PABPN1 mRNA decay inskeletal muscle compared to kidney.

ResultsHere, we show that the steady-state levels of both PABPN1 mRNA and protein aredrastically lower in mouse and human skeletal muscle, particularly those impactedin OPMD, compared to other tissues. In contrast, PABPN1 levels are increasedduring muscle regeneration, suggesting a greater requirement for PABPN1 functionduring tissue repair. Further analysis indicates that modulation of PABPN1expression is likely due to post-transcriptional mechanisms acting at the level ofmRNA stability.

ConclusionsOur results demonstrate that PABPN1 steady-state levels and likely control ofexpression differ significantly in skeletal muscle as compared to other tissues,which could have important implications for understanding the muscle-specificnature of OPMD.

KeywordsPABPN1 OPMD Skeletal muscle Muscular dystrophy Polyalanine expansion AbbreviationsAREAU-rich element

GAPDHglyceraldehyde-3-phosphate dehydrogenase

HSP90Heat shockprotein 90

OPMDOculopharyngeal muscular dystrophy

PABPN1Nuclear polyA-bindingprotein 1

PGC1αPeroxisome proliferator-activated receptor gamma, coactivator1α

qRT PCRQuantitative real-time polymerase chain reaction

RACERapidamplification of cDNA ends

UTRUntranslated region.

Electronic supplementary materialThe online version of this article doi:10.1186-2044-5040-3-23 contains supplementary material, which is available to authorized users.

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Author: Luciano H Apponi - Anita H Corbett - Grace K Pavlath


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