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Review
, 12 (1), 429-35

Ageing and the Small, Non-Coding RNA World

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Review

Ageing and the Small, Non-Coding RNA World

Masaomi Kato et al. Ageing Res Rev.

Abstract

MicroRNAs, a class of small, non-coding RNAs, are now widely known for their importance in many aspects of biology. These small regulatory RNAs have critical functions in diverse biological events, including development and disease. Recent findings show that microRNAs are essential for lifespan determination in the model organisms, Caenorhabditis elegans and Drosophila, suggesting that microRNAs are also involved in the complex process of ageing. Further, short RNA fragments derived from longer parental RNAs, such as transfer RNA cleavage fragments, have now emerged as a novel class of regulatory RNAs that inhibit translation in response to stress. In addition, the RNA editing pathway is likely to act in the double-stranded RNA-mediated silencing machinery to suppress unfavorable RNA interference activity in the ageing process. These multiple, redundant layers in gene regulatory networks may make it possible to both stably and flexibly regulate genetic pathways in ensuring robustness of developmental and ageing processes.

Figures

Figure 1
Figure 1
A model for miRNA-mediated regulation of ageing pathways: The lin-4 miRNA and its target lin-14, and miR-239 seem to regulate lifespan indirectly by modifying the insulin-signaling pathway (dashed lines). miR-71 appears to directly affect the insulin-signaling and DNA damage response pathways.
Figure 2
Figure 2
A novel non-coding RNA role for tRNA-derived RNA fragments: A specific ribonuclease cleaves tRNA transcripts in response to stress (e.g. heat or oxidative stress), producing a nearly half-sized tRNA fragments (half-tRNAs). A subset of 5’ half-tRNAs cooperates with a translational silencer complex to inhibit translational initiation.
Figure 3
Figure 3
Antagonistic function of RNA editing in RNAi machinery: ADAR activity can modify target specificity of miRNAs or siRNAs, or transcripts of protein-coding genes. In addition, ADAR activity may prevent dsRNAs from entering the RNAi pathway by introducing RNA modifications (shown by red circles) that reduce the self-complementarity of the dsRNAs – a requirement for effective RNAi. This hypothesis is based on the observation that loss of RNA editing activity (RNAe) results in an accumulation of siRNA species and an increase in certain forms of RNAi-mediated gene silencing, but the silencing activity is suppressed by loss of an RNAi component.

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