The Heart of Stress Responses

Science's STKE  01 May 2007:
Vol. 2007, Issue 384, pp. tw153
DOI: 10.1126/stke.3842007tw153

Two myosin heavy chain (MHC) genes are expressed in opposing manners in the mouse heart; βMHC is expressed embryonically, whereas αMHC is up-regulated postnatally. Cardiac stress shifts this ratio toward βMHC with negative effects on cardiac function, and previous work has identified microRNAs (miRNAs) as possible regulators of cardiac growth and function. Van Rooij et al. now show that miR-208, which is encoded by an intron of the αMHC gene, is a cardiac-specific regulator of βMHC expression in response to stress and hypothyroidism in the heart. Deletion of the coding region of miR-208 resulted in inhibition of βMHC expression and a reduced stress response in the heart. Thus, miR-208 may act through thyroid signaling to regulate βMHC expression, possibly by repressing expression of the thyroid receptor coregulator THRAP1.

E. van Rooij, L. B. Sutherland, X. Qi, J. A. Richardson, J. Hill, E. N. Olson, Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316, 575-579 (2007). [Abstract] [Full Text]