A microRNA feedback loop regulates global microRNA abundance during aging
A microRNA feedback loop regulates global microRNA abundance during aging
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DOI：
10.1261/rna.062190.117
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发表时间：
2018-02-01
期刊：
影响因子：
4.5
通讯作者：
Slack, Frank J.
中科院分区：
文献类型：
--
作者：
Inukai, Sachi;Pincus, Zachary;Slack, Frank J.
许多microRNA（miRNAs）的表达水平在衰老过程中发生变化，在许多生物体和组织中显著下降。然而，人们对这种变化的机制或生物学意义知之甚少。我们研究了C. elegans老化我们发现，miRNA生物发生基因与转录因子和衰老相关的miRNA高度网络化。具体而言，已知影响寿命且自身在衰老过程中上调的miR-71在衰老过程中转录后抑制alg-1/Argonaute表达。mir-71功能缺失突变体中ALG-1丰度的增加导致miRNA表达的整体增加。有趣的是，这些突变体表现出广泛的mRNA表达失调和基因表达和整体寿命的变异水平降低。因此，进行性分子衰退通常被认为是生物体一生中累积损伤的结果，这可能部分由年龄相关衰退的miRNA指导机制解释。
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.