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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Sequence variants within the 3'-UTR of the COL5A1 gene alters mRNA stability: Implications for musculoskeletal soft tissue injuries
Matrix Biology, Volume 30, No. 5-6, Year 2011
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Description
COL5A1 encodes the α1 chain of type V collagen, a quantitatively minor fibrillar collagen that regulates fibrillogenesis. A variant within the 3'-UTR of COL5A1 is associated with chronic Achilles tendinopathy (AT) and other exercise-related phenotypes but the functional significance of this is unknown. The aim of this study was therefore to identify functional differences between the COL5A1 3'-UTR from patients with AT and asymptomatic controls. To this end we have used a reporter assay in which the COL5A1 3'-UTR from AT patients and controls were cloned downstream of the firefly luciferase gene and luciferase activity measured as an indication of mRNA stability. When the cloned COL5A13'-UTRs were sequenced, two major forms named C- and T-alleles were predominantly identified in the controls and the AT subjects respectively. The luciferase activity of the C-alleles was significantly lower than that of the T-alleles (69.0 ± 22.0% (N=24) vs. 90.6 ± 13.7% (N=30), p<0.001) which suggests an overall increase in mRNA stability for the T-allele. Furthermore, we identified a functional miRNA site for Hsa-miR-608 within the COL5A1 3'-UTR and using deletion constructs we have identified additional elements which regulate COL5A1 mRNA stability. These results have important implications for our understanding of the molecular basis of musculoskeletal soft tissue injuries and other exercise-related phenotypes. © 2011 International Society of Matrix Biology.
Authors & Co-Authors
Laguette, Mary Jessica
South Africa, Cape Town
University of Cape Town
Abrahams, Yoonus
South Africa, Cape Town
University of Cape Town
Prince, Sharon
South Africa, Cape Town
University of Cape Town
Collins, Malcolm R.
South Africa, Cape Town
University of Cape Town
South Africa, Tygerberg
South African Medical Research Council
Statistics
Citations: 94
Authors: 4
Affiliations: 2
Identifiers
Doi:
10.1016/j.matbio.2011.05.001
ISSN:
0945053X
e-ISSN:
15691802
Research Areas
Genetics And Genomics
Violence And Injury