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It is also worth mentioning that multiple components of the InsR pathway, including age-1, pdk-1, akt-2, and daf-16, are predicted to be targets of the let-7 family miRNAs. On one hand, we showed that deletions of a good number of miRNAs have varying impacts on the L1 diapause survival rate, although they may effect the rate through different mechanisms. Instead, many specific physiological functions, such as the starvation-induced stress response, are regulated by a miRNA-target network, often involving multiple miRNAs and a large number of their targets. This is consistent with hbl-1 being one of the downstream targets of miR-71, although this modest effect alone is not expected to account for the vulval developmental phenotype in mir-71 mutant. Moreover, the expression of hbl-1 is repressed by let-7 family miRNAs at L3 during normal development, and the hyperactivity of hbl-1 caused by failure of miRNA regulation leads to retarded development (26). (A) Differential interference contrast (DIC) images showing L4 worms recovered from 4-d–starved L1 worms.

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