MiRNAs are small, noncoding RNAs (20-23 nucleotides) that bind to complementary sequences in mRNAs and thereby induce their degradation or translational repression. 20 years after their discovery, it is more than ever evident how important miRNAs are for the regulation of gene expression. They control essential processes in higher eukaryotes, such as development, metabolism and the iimmune system. In addition, miRNAs are involved in cancer, cardiovascular diseases and others. However, our understanding of miRNA functions is hampered by the intrinsic mechanism of miRNAs: next to their embedding into their functional unit, the miRISC ribonucleoprotein complex, only 6-8 nucleotides of a miRNA determine mRNA recognition. Given this, bioinformatic analyses predict a plethora of target mRNAs, interactions and levels of regulation: i.) almost every mRNA contains miRNA binding sites, ii.) various mRNAs may carry sites for an individual miRNA, and iii.) one mRNA may contain sites for various miRNAs. Based on these predictions we may expect an enormous complexity in miRNA-dependent regulatory networks. This complexity could be required to fine-tune or to boost the cellular response to an external stimulus - either on a single mRNA or through cascades of miRNA regulation on different levels within a pathway. The topic of this BioSysNet research group is the functional characterization of cardiovascular miRNAs and their interactions in cardiovascular disease.

... coming soon

Engelhardt S, Leierseder S (2013). Coinciding functions for miR-145 in vascular smooth muscle and cardiac fibroblasts. J Mol Cell Cardiol 65:105-7. 

Rinck A, Preusse M, Laggerbauer B, Lickert H, Engelhardt S, Theis FJ (2013). The human transcriptome is enriched for miRNA-binding sites located in cooperativity-permitting distance. RNA Biol 10(7):1125-35. 

Ganesan J, Ramanujam D, Sassi Y, Ahles A, Jentzsch C, Werfel S, Leierseder S, Loyer X, Giacca M, Zentilin L, Thum T, Laggerbauer B, Engelhardt S (2013). MiR-378 controls cardiac hypertrophy by combined repression of mitogen-activated protein kinase pathway factors. Circulation 127(21):2097-106. 

Hulot JS, Fauconnier J, Ramanujam D, Chaanine A, Aubart F, Sassi Y, Merkle S, Cazorla O, Ouillé A, Dupuis M, Hadri L, Jeong D, Mühlstedt S, Schmitt J, Braun A, Bénard L, Saliba Y, Laggerbauer B, Nieswandt B, Lacampagne A, Hajjar RJ, Lompré AM & Engelhardt S. Critical role for stromal interaction molecule 1 in cardiac hypertrophy. Circulation 124, 796-805 (2011).

Ahles A, Rochais F, Frambach T, Bünemann M & Engelhardt S. A polymorphism-specific "memory" mechanism in the β(2)-adrenergic receptor. Science Signal. 4, ra53 (2011).

Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J & Engelhardt S. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456, 980-984 (2008).

Rochais F, Vilardaga JP, Nikolaev VO, Bünemann M, Lohse MJ & Engelhardt S. Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. J. Clin. Invest. 117, 229-235 (2007).

Buitrago M, Lorenz K, Maass AH, Oberdorf-Maass S, Keller U, Schmitteckert EM, Ivashchenko Y, Lohse MJ & Engelhardt S. The transcriptional repressor NAB1 is a specific regulator of pathological cardiac hypertrophy. Nat. Med. 11, 837-844 (2005).