TY - JOUR
T1 - A microRNA feedback loop regulates global microRNA abundance during aging
AU - Inukai, Sachi
AU - Pincus, Zachary
AU - De Lencastre, Alexandre
AU - Slack, Frank J.
N1 - Funding Information:
We would like to thank Rob Mitra (Washington University in St. Louis) for helpful discussions on gene expression variability. We also thank the Bioinformatics Core at Harvard School of Public Health for their help with RNA-seq data processing; computations for this project were run on the Yale Biomedical HPC and Harvard Medical School HPC. We also thank Chanatip Metheetrairut and members of the Slack laboratory for helpful discussions and critical reading of the manuscript. F.J.S. was funded by National Institutes of Health R01 AG033921; Z.P. was funded by National Insitutes of Health R00 AG042487. Some C. elegans strains were provided by the CGC, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440).
Publisher Copyright:
© 2018 Inukai et al.
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - Aging
KW - Argonaute
KW - Caenorhabditis elegans
KW - MiR-71
KW - MicroRNAs
UR - http://www.scopus.com/inward/record.url?scp=85040971833&partnerID=8YFLogxK
U2 - 10.1261/rna.062190.117
DO - 10.1261/rna.062190.117
M3 - Article
C2 - 29114017
AN - SCOPUS:85040971833
SN - 1355-8382
VL - 24
SP - 159
EP - 172
JO - RNA
JF - RNA
IS - 2
ER -