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Predicting the lifespan

Across metazoans, lifespan varies greatly, not only among species but also within the same species. Much effort has been devoted to discovering genetic and abiotic factors associated with longevity in humans, and many lifespan-extending perturbations in model organisms like C. elegans have been discovered. Interestingly enough, homogenous genetically identical C. elegans are equally variable as the outbred human population.

In this recently published article (Kinser et al 2021) from Zachary Pincus lab, authors propose that this mode of inter-individual differences may be due to the change in the expression of key regulatory genes. To address or test this model, they used the expression of 22 miRNA promoter-driven GFP and predicted the future lifespan of animals. Intriguingly, the authors found that almost 50% of these reporters could effectively predict the lifespan of animals till they died. Moreover, 2 of these reporters (miR-47 and miR-243) that are most accurate in predicting lifespan, are involved in gene regulatory processes that do not require DAF-16/FOXO transcription factor.

Finally, they also show that three of these transgenes (miR-240-786, miR-793, and miR-47) that are expressed in different tissues, and show a differential pattern throughout life, provide redundant information about a single lifespan determinant process. This process is most probably a cell non-autonomous one that does not depend on DAF-16.

Kinser, H. E., Mosley, M. C., Plutzer, I. B. and Pincus, Z. (2021) Global, cell non-autonomous gene regulation drives individual lifespan among isogenic C. elegans. eLife; 10:e65026. DOI: https://doi.org/10.7554/eLife.65026

let-7 microRNA absent in many Caenorhabditis nematodes

A recent paper by Nelson and Ambros [1] reports that let-7 heterochronic microRNA is absent in Caenorhabditis species of the japonica group. Research in C. elegans has shown that let-7 plays an essential role during larval to adult transition and mutations in let-7 cause lethality. Authors used one species of the japonica group, C. sulstoni, to further investigate microRNA gene regulatory network. The results revealed that the loss of let-7 function in this species is compensated by other let-7 family members, i.e., miR-48, miR- 84, and miR-241.

Considering that let-7 is highly conserved across bilaterians [2], the results presented in this paper are exciting. However, more work is needed to understand the basis of such an evolutionary change and other potential changes in microRNA-mediated processes.

1. Nelson C. and Ambros V. (2021). A cohort of Caenorhabditis species lacking the highly conserved let-7 microRNA. G3, 11(3), jkab022. DOI: 10.1093/g3journal/jkab022.

2. Pasquinelli A.E. et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 408:86–89.