Messenger RNA degradation may be inhibited in sporadic inclusion body myositis.
OBJECTIVE
To integrate an immune-mediated mechanism and the disturbed protein expression in sporadic inclusion body myositis (IBM).


BACKGROUND
In IBM, abnormal fibers harbor inclusions of some proteins found in the brains of patients with Alzheimer disease (AD). Poly(A)-binding protein 1 (PABP1) is the RNA binding protein that attaches to the poly(A) tail of mRNA and is involved in translation and mRNA degradation. Under stresses, mRNA combined with PABP1 forms cytoplasmic granules called stress granules.


METHODS
Using 12 muscle biopsies with sporadic IBM and 46 controls, the authors localized PABP1 by immunohistochemistry, and poly(A)-containing RNA (poly(A)+ RNA) using the in situ hybridization method. They also immuno-localized HuR, one of the components of stress granules.


RESULTS
In IBM, a proportion of fibers, including those vacuolated, showed an abnormal accumulation of PABP1 immuno-positive deposits. An immunofluorescence study indicated that large PABP1 positive deposits formed conglomerates with poly(A)+ RNA and PABP1 colocalized with HuR. Although PABP1-positive cytoplasmic inclusions were found in disease controls, their aggregates combined with poly(A)+ RNA were only detected in IBM.


CONCLUSIONS
The localization of PABP1 positive deposits in inclusion body myositis (IBM) and other diseases may correspond to the stress granules that are formed under exposure to cellular stresses and the sites of mRNA turnover. The concomitant aggregation of poly(A)+ RNA that is specifically found in IBM may be due to the inhibition of mRNA degradation, which may affect translation. The authors speculate that an autoantibody against mRNA degradation machinery could play a role in this inhibition.
Nakano
S
S
Department of Neurology, Kansai Medical University, Moriguchi-city, Japan. nakanos@takii.kmu.ac.jp
Shinde
A
A
Ito
H
H
Ito
H
H
Kusaka
H
H
D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D015415:Biomarkers; D001706:Biopsy; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018979:Myositis, Inclusion Body / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D014176:Protein Biosynthesis / Q000235:genetics / Q000276:immunology; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism
D001323:Autoantibodies; D015415:Biomarkers; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger