Pandit, A. and Jain, V. and Kumar, N. (2014) PHA-4/FOXA-regulated microRNA feed forward loops during Caenorhabditis elegans dietary restriction. Aging Us, 6 (10). p. 835.

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Abstract

Dietary restriction (DR) increases life span and delays the onset of age-related diseases across species. However, the molecular mechanisms have remained relatively unexplored in terms of gene regulation. In C. elegans, a popular model for aging studies, the FOXA transcription factor PHA-4 is a robust genetic regulator of DR, although little is known about how it regulates gene expression. We profiled the transcriptome and miRNAome of an eat-2 mutant, a genetic surrogate of DR, by Next Generation sequencing and find that most of the miRNAs are upregulated in the young-adult worms, none significantly downregulated. Interestingly, PHA-4 can potentially regulate the expression of most of these miRNA genes. Remarkably, many of the PHA-4-regulated genes that are induced during DR are also targets of the PHA-4-upregulated miRNAs, forming a large feed-forward gene regulatory network. The genes targeted by the feed-forward loops (FFLs) are enriched for functions related to ubiquitin-mediated decay, lysosomal autophagy, cellular signalling, protein folding etc., processes that play critical roles in DR and longevity. Together our data provides a framework for understanding the complex and unique regulatory network employed during DR, suggesting that PHA-4 employs such FFLs to fine-tune gene expression and instil robustness in the system during energy crisis.

Item Type:	Article
Subjects:	Genetics
Depositing User:	Unnamed user with email alok@urdip.res.in
Date Deposited:	31 Mar 2015 10:51
Last Modified:	31 Mar 2015 10:51
URI:	http://nii.sciencecentral.in/id/eprint/11

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