Role of post‐transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease

Chronic kidney disease (CKD) represents an important public health problem. Its progression to end-stage renal disease is associated with increased morbidity and mortality. The determinants of renal function decline are not fully understood. Recent progress in the understanding of post-transcriptional regulation of mRNA stability has helped the identification of both the trans-and cis-acting elements of mRNA as potential markers and therapeutic targets for difficult-to-diagnose and -treat diseases, including CKDs such as diabetic nephropathy. Human antigen R (HuR), a trans-acting element of mRNA, is an RNA binding factor (RBF) best known for its ability to stabilize AU-rich-element-containing mRNAs. Deregulated HuR subcellular localization or expression occurs in a wide range of renal diseases, such as metabolic acidosis, ischemia, and fibrosis. Besides RBFs, recent evidence revealed that noncoding RNA, such as microRNA and long noncoding RNA, participates in regulating mRNA stability and that aberrant noncoding RNA expression accounts for many pathologic renal conditions. The goal of this review is to provide an overview of our current understanding of the post-transcriptional regulation of mRNA stability in renal pathophysiology and to offer perspectives for this class of diseases. We use examples of diverse renal diseases to illustrate different mRNA stability pathways in specific cellular compartments and discuss the roles and impacts of both the cis-and trans-activating factors on the regulation of mRNA stability in these diseases.—Feigerlovà, E., Battaglia-Hsu, S.-F. Role of post-transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease. FASEB J. 31, 457–468 (2017). www.fasebj.org