A microRNA feedback loop regulates global microRNA abundance during aging
- 1Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, Connecticut 06520, USA
- 2Institute for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
- 3Department of Developmental Biology
- 4Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA
- Corresponding author: fslack{at}bidmc.harvard.edu
Abstract
Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence life span and itself up-regulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging. Increased ALG-1 abundance in mir-71 loss-of-function mutants led to globally increased miRNA expression. Interestingly, these mutants demonstrated widespread mRNA expression dysregulation and diminished levels of variability both in gene expression and in overall life span. Thus, the progressive molecular decline often thought to be the result of accumulated damage over an organism's life may be partially explained by a miRNA-directed mechanism of age-associated decline.
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.062190.117.
- Received May 22, 2017.
- Accepted October 29, 2017.
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