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Project B4: Regulatory circuits involving miRNA-mediated repression of MAL/MRTF-A in muscle cells

Supervisor: Prof. Dr. Guido Posern

Specific aims/topics:

  1. The regulation of MAL/MRTF-A and its target genes by microRNAs

  2. Understanding the miRNA-MRTF circuitry in muscle cell differentiation

     

Background and significance:

Complex processes of differentiation from precursor cells are necessary to generate smooth muscle and skeletal muscle tissue. In both cases the ubiquitous serum response factor (SRF) is an important transcription factor for muscle specific gene expression. The Myocardin-related transcription factor A (MRTF-A) is a coactivator of SRF, enabling specific gene expression patterns. It could be shown that MRTF-A is expressed in undifferentiated myoblast cells and in synthetic SMCs. In differentiated cells, however, the expression of MRTF-A is decreased. Nevertheless MRTF-A is necessary for differentiation of muscle cells. Together with SRF MRTF-A controls various muscle-specific genes like SM22α, smooth muscle myosin, smooth muscle α-actin, SM MHC, skeletal α-actin and skeletal α-MHC. Latest data showed that MRTF-A in smooth muscle cells is posttranscriptionally regulated by miRNA-1, one of several miRNAs expressed in muscle tissues, revealing a new way of regulating MRTF-A activity. This raises the question whether further miRNAs exist able to posttranscriptionally regulate MRTF-A.