Other
13 Authors
- Mao L,
- Kim IM,
- Johnson JA,
- Traynham CJ,
- Tang Y,
- Rockman HA,
- Koch WJ,
- Park KM,
- Pironti G,
- Vinson J,
- Wang Y,
- Su H,
- Teoh JP
| First Author | Kim IM | Year | 2014 |
| Journal | Circ Res | Volume | 114 |
| Issue | 5 | Pages | 833-44 |
| PubMed ID | 24334028 | Mgi Jnum | J:223705 |
| Mgi Id | MGI:5660092 | Doi | 10.1161/CIRCRESAHA.114.302766 |
| Citation | Kim IM, et al. (2014) beta-arrestin1-biased beta1-adrenergic receptor signaling regulates microRNA processing. Circ Res 114(5):833-44 |
| abstractText | RATIONALE: MicroRNAs (miRs) are small, noncoding RNAs that function to post-transcriptionally regulate gene expression. First transcribed as long primary miR transcripts (pri-miRs), they are enzymatically processed in the nucleus by Drosha into hairpin intermediate miRs (pre-miRs) and further processed in the cytoplasm by Dicer into mature miRs where they regulate cellular processes after activation by a variety of signals such as those stimulated by beta-adrenergic receptors (betaARs). Initially discovered to desensitize betaAR signaling, beta-arrestins are now appreciated to transduce multiple effector pathways independent of G-protein-mediated second messenger accumulation, a concept known as biased signaling. We previously showed that the beta-arrestin-biased betaAR agonist, carvedilol, activates cellular pathways in the heart. OBJECTIVE: Here, we tested whether carvedilol could activate beta-arrestin-mediated miR maturation, thereby providing a novel potential mechanism for its cardioprotective effects. METHODS AND RESULTS: In human cells and mouse hearts, carvedilol upregulates a subset of mature and pre-miRs, but not their pri-miRs, in beta1AR-, G-protein-coupled receptor kinase 5/6-, and beta-arrestin1-dependent manner. Mechanistically, beta-arrestin1 regulates miR processing by forming a nuclear complex with hnRNPA1 and Drosha on pri-miRs. CONCLUSIONS: Our findings indicate a novel function for beta1AR-mediated beta-arrestin1 signaling activated by carvedilol in miR biogenesis, which may be linked, in part, to its mechanism for cell survival. |
