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Trends Cardiovasc Med. 2015 Nov;25(8):676-83. doi: 10.1016/j.tcm.2015.02.006. Epub 2015 Feb 20.

RNA-stabilizing proteins as molecular targets in cardiovascular pathologies.

Author information

1
Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX.
2
Department of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX. Electronic address: pkrishnamurthy@houstonmethodist.org.

Abstract

The stability of mRNA has emerged as a key step in the regulation of eukaryotic gene expression and function. RNA stabilizing proteins (RSPs) contain several RNA recognition motifs, and selectively bind to adenylate-uridylate-rich elements in the 3' untranslated region of several mRNAs leading to altered processing, stability, and translation. These post-transcriptional gene regulations play a critical role in cellular homeostasis; therefore act as molecular switch between 'normal cell' and 'disease state.' Many mRNA binding proteins have been discovered to date, which either stabilize (HuR/HuA, HuB, HuC, HuD) or destabilize (AUF1, tristetraprolin, KSRP) the target transcripts. Although the function of RSPs has been widely studied in cancer biology, its role in cardiovascular pathologies is only beginning to evolve. The current review provides an overall understanding of the potential role of RSPs, specifically HuR-mediated mRNA stability in myocardial infarction, hypertension and hypertrophy. Also, the effect of RSPs on various cellular processes including inflammation, fibrosis, angiogenesis, cell-death, and proliferation and its relevance to cardiovascular pathophysiological processes is presented. We also discuss the potential clinical implications of RSPs as therapeutic targets in cardiovascular diseases.

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PMID:
25801788
PMCID:
PMC4545469
DOI:
10.1016/j.tcm.2015.02.006
[Indexed for MEDLINE]
Free PMC Article

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