miR-34a and the Cardiomyopathy of Senescence: SALT PNUTS, SALT PNUTS!

Abstract

The search for eternal youth is as old as mankind. In a recent Nature paper, Boon et al find that miR34 and its mRNA target PNUTS mediate DNA damage repair and provoke cardiac senescence. Interrupting the miR-34a/PNUTS pathway promises to favorably modify age- and stress-induced cardiac degeneration[AG1] (Boon et al., 2013). “Middle age ends and senescence begins, the day your descendants outnumber your friends.” Ogden Nash. “It’s not the years, Honey, it’s the mileage.” Indiana Jones from Raiders of the Lost Ark.

Macrophage migration inhibitory factor serves a pivotal role in�the regulation of radiation-induced cardiac senescencethrough rebalancing the microRNA-34a/sirtuin 1 signaling pathway

“…miRs have emerged as a new class of modulators of gene expression. Among these, miR-34a has been implicated in cardiac-associated damage, particularly cardiac senescence (31). Researchers recently demonstrated that miR-34a was involved in modulating radiation-induced senescence, and that radiation-induced senescence was correlated with the upregulation of miR-34a expression (32).…”

miR-34a inhibits migration and invasion by regulating the SIRT1/p53 pathway in human SW480 cells

“…miR-34a maps to the 1p36 genomic region in humans, and is expressed at higher levels compared to other family members. Several studies have indicated that upregulation of miR-34a can induce apoptosis, senescence, differentiation, cell-cycle arrest, and growth suppression ( 8 – 10 ). The abnormal expression of miR-34a results in cell-cycle arrest, growth inhibition and attenuated chemoresistance to antitumor drugs.…”

Biophysical Analysis of the N-Terminal Domain from the Human Protein Phosphatase 1 Nuclear Targeting Subunit PNUTS Suggests an Extended Transcription Factor TFIIS-Like Fold

“…Human PNUTS (PP1 Nuclear Targeting Protein) is a Protein Phosphatase 1 (PP1) binding protein with critical functions in the response to cellular stresses, including DNA damage, and the regulation of RNA-polymerase II -mediated gene expression [1][2][3][4][5]. It forms a ternary complex with PP1, Tox4 and WDR82 that targets PP1 to the nucleus [3][4][5][6][7][8][9][10], and further interacts with the tumour suppressor phosphatase and tensin homolog PTEN [11].…”

“…It forms a ternary complex with PP1, Tox4 and WDR82 that targets PP1 to the nucleus [3][4][5][6][7][8][9][10], and further interacts with the tumour suppressor phosphatase and tensin homolog PTEN [11].…”