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Int J Clin Exp Pathol 2013;6(9):1723-1733
Original Article
Investigation of splicing changes and post-translational processing of LMNA in sporadic
inclusion body myositis
Yue-Bei Luo, Chalermchai Mitrpant, Russell Johnsen, Vicki Fabian, Merrilee Needham, Sue Fletcher, Steve D Wilton, Frank L Mastaglia
Centre for Neuromuscular and Neurological Disorders, Australian Neuro-Muscular Research Institute, University of Western Australia, Perth,
Australia; Laboratory of Neuromuscular Disorders, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China; Department of
Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Section of Neuropathology, Department of Anatomical
Pathology, Royal Perth Hospital, Perth, Australia; Centre for Comparative Genomics, Murdoch University, Perth, Australia; Institute for
Immunology & Infectious Diseases, Murdoch University, Perth, Australia
Received July 17, 2013; Accepted August 11, 2013; Epub August 15, 2013; Published September 1, 2013
Abstract: Some features of sporadic inclusion body myositis (s-IBM) suggest that there is acceleration of the normal ageing process in muscle
tissue. LMNA encodes the nuclear lamina proteins lamin A/C through alternative splicing, and aberrant splicing of exon 11 leads to the
premature ageing disease, Hutchinson-Gilford progeria syndrome. Progerin, the pathogenic isoform expressed in HGPS tissues, has also
been detected at low levels in tissues of normal individuals with aging. We therefore investigated the alternative splicing of LMNA gene
transcripts, and the post-translational processing of prelamin A, in s-IBM and control muscle samples. Age-related low level expression of the
progerin transcript was detected in both s-IBM and control muscles, but was not increased in s-IBM and there was no increase in progerin
protein or demonstrable accumulation of intermediate prelamin isoforms in the s-IBM muscles. However, an age-related shift in the balance of
splicing towards lamin A-related transcripts, which was present in normal muscles, was not found in s-IBM. Our findings indicate that while
there are changes in the patterns of LMNA splicing in s-IBM muscle which are probably secondary to the underlying pathological process, it is
unlikely that aberrant splicing of exon 11 or defective post-translational processing of prelamin A are involved in the pathogenesis of the
disease. (IJCEP1307031).
Keywords: Inclusion body myositis, muscle, LMNA, progerin, prelamin A, lamin A/C
Address correspondence to: Dr. Frank L Mastaglia, Australian Neuro-Muscular Research Institute, University of Western Australia, Perth,
Australia. Tel: +61 93462818; Fax: +61 93463487; E-mail: francis.mastaglia@anri.uwa.edu.au
Original Article
Investigation of splicing changes and post-translational processing of LMNA in sporadic
inclusion body myositis
Yue-Bei Luo, Chalermchai Mitrpant, Russell Johnsen, Vicki Fabian, Merrilee Needham, Sue Fletcher, Steve D Wilton, Frank L Mastaglia
Centre for Neuromuscular and Neurological Disorders, Australian Neuro-Muscular Research Institute, University of Western Australia, Perth,
Australia; Laboratory of Neuromuscular Disorders, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China; Department of
Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Section of Neuropathology, Department of Anatomical
Pathology, Royal Perth Hospital, Perth, Australia; Centre for Comparative Genomics, Murdoch University, Perth, Australia; Institute for
Immunology & Infectious Diseases, Murdoch University, Perth, Australia
Received July 17, 2013; Accepted August 11, 2013; Epub August 15, 2013; Published September 1, 2013
Abstract: Some features of sporadic inclusion body myositis (s-IBM) suggest that there is acceleration of the normal ageing process in muscle
tissue. LMNA encodes the nuclear lamina proteins lamin A/C through alternative splicing, and aberrant splicing of exon 11 leads to the
premature ageing disease, Hutchinson-Gilford progeria syndrome. Progerin, the pathogenic isoform expressed in HGPS tissues, has also
been detected at low levels in tissues of normal individuals with aging. We therefore investigated the alternative splicing of LMNA gene
transcripts, and the post-translational processing of prelamin A, in s-IBM and control muscle samples. Age-related low level expression of the
progerin transcript was detected in both s-IBM and control muscles, but was not increased in s-IBM and there was no increase in progerin
protein or demonstrable accumulation of intermediate prelamin isoforms in the s-IBM muscles. However, an age-related shift in the balance of
splicing towards lamin A-related transcripts, which was present in normal muscles, was not found in s-IBM. Our findings indicate that while
there are changes in the patterns of LMNA splicing in s-IBM muscle which are probably secondary to the underlying pathological process, it is
unlikely that aberrant splicing of exon 11 or defective post-translational processing of prelamin A are involved in the pathogenesis of the
disease. (IJCEP1307031).
Keywords: Inclusion body myositis, muscle, LMNA, progerin, prelamin A, lamin A/C
Address correspondence to: Dr. Frank L Mastaglia, Australian Neuro-Muscular Research Institute, University of Western Australia, Perth,
Australia. Tel: +61 93462818; Fax: +61 93463487; E-mail: francis.mastaglia@anri.uwa.edu.au
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