# Roquin Modulates Cardiac Post-Infarct Remodeling via microRNA Stability Control

## TL;DR

Roquin proteins control microRNA stability in heart cells, affecting recovery after heart attacks by regulating the transcription factor ZBTB20.

## Contribution

This study identifies miR-23b-5p as a Roquin-regulated microRNA that influences post-infarct cardiac recovery via ZBTB20.

## Key findings

- Roquin-1 and Roquin-2 are downregulated in hypoxia, affecting miRNA stability.
- miR-23b-5p levels increase with Roquin-2 down-regulation and target ZBTB20.
- Antagomir against miR-23b-5p reverses ZBTB20 down-regulation under hypoxia.

## Abstract

Through binding to complementary mRNAs, microRNAs (miRNAs) mediate gene silencing. The stability and half-life of microRNAs are controlled by two isoforms of the RNA-binding protein Roquin. This study aimed at identifying the role of Roquin to miRNA-dependent regulation of the transcriptome in the post-ischemic heart. Both Roquin isoforms are highly conserved between rats and humans and constitutively expressed in cardiomyocytes. In both cell species, hypoxia induces a down-regulation of Roquin-1 and Roquin-2. An integrative miRNA-and-mRNA analysis (MMIA) identified miR-23b-5p as a potential interaction partner of Roquins. The open data bank TargetScan8.0 suggests that the transcription factor ZBTB20 is a potential target of miR-23b-5p. The level of expression of ZBTB20 correlated with the functional recovery of rat hearts after myocardial infarction. Moreover, the down-regulation of Roquin-2 in AC16 cells by siRNA under normoxic conditions was associated with an up-regulation of miR-23b-5p and a down-regulation of ZBTB20. Furthermore, in the case of hypoxia-dependent down-regulation of Roquin, the subsequent down-regulation of ZBTB20 was reversed with the help of an antagomir against miR-23b-5p. In conclusion, hypoxia-induced down-regulation of the two Roquin isoforms was associated with an increased stability of miR-23b-5p, a Roquin-2-dependent miRNA, which subsequently led to silencing of the transcription factor ZBTB20.