The 3' Untranslated Region Protects the Heart from Angiotensin II-Induced Cardiac Dysfunction via AGGF1 Expression.

The messenger RNA (mRNA) 3' untranslated regions as cis-regulated elements bound by microRNAs (miRNAs), affect their gene translation. However, the role of the trans-regulation of during heart dysfunction remains elusive. Compared with administration of angiogenic factor with G-patch and forkhead-associate domains 1 (Aggf1), ectopic expression of Aggf1 with its significantly suppressed cardiac dysfunction in angiotensin II-infused mice, with upregulated expression of both Aggf1 and myeloid cell leukemia 1 (Mcl1). Along their Mcl1 and Aggf1 mRNAs share binding sites for the same miRNAs, including miR-105, miR-101, and miR-93. We demonstrated that the protein-coding Mcl1 and Aggf1 mRNAs communicate and co-regulate each other's expression through competition for these three miRNAs that target both transcripts via their Our results indicate that Aggf1 as a trans-regulatory element, accelerates the cardioprotective role of Aggf1 in response to hypertensive conditions by elevating Mcl1 expression. Our work broadens the scope of gene therapy targets and provides a new insight into gene therapy strategies involving

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