Cyclic stretch increases splicing noise rate in cultured human fibroblasts
1 Institute of Human Genetics, University of Ulm, Albert Einstein Allee 11, D 89070 Ulm, Germany
2 ZWE Biomaterials, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, D 70569 Stuttgart, Germany
3 Department New Materials and Biosystems, Max Planck Institute for Intelligent Systems, Heisenbergstrasse 3, D 70569 Stuttgart, Germany
4 Biophysical Chemistry, University of Heidelberg, INF 253, D 69120 Heidelberg, Germany
BMC Research Notes 2011, 4:470 doi:10.1186/1756-0500-4-470Published: 31 October 2011
Mechanical forces are known to alter the expression of genes, but it has so far not been reported whether they may influence the fidelity of nucleus-based processes. One experimental approach permitting to address this question is the application of cyclic stretch to cultured human fibroblasts. As a marker for the precision of nucleus-based processes, the number of errors that occur during co-transcriptional splicing can then be measured. This so-called splicing noise is found at low frequency in pre-mRNA splicing.
The amount of splicing noise was measured by RT-qPCR of seven exon skips from the test genes AATF, MAP3K11, NF1, PCGF2, POLR2A and RABAC1. In cells treated by altered uniaxial cyclic stretching for 18 h, a uniform and significant increase of splicing noise was found for all detectable exon skips.
Our data demonstrate that application of cyclic stretch to cultured fibroblasts correlates with a reduced transcriptional fidelity caused by increasing splicing noise.