AID-ing Up MicroRNA Functions

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Science  27 Jun 2008:
Vol. 320, Issue 5884, pp. 1696
DOI: 10.1126/science.320.5884.1696a

MicroRNAs are key regulators of gene function, yet the full scope of their influence is not known. In the immune system, miR-155 has multiple roles, although B cells show a particular dependence on its effects. Two studies now provide evidence that this is largely due to its targeting of the enzyme activation-induced cytidine deaminase (AID), which regulates somatic hypermutation and class-switch recombination of antibody genes.

After identifying miR-155 response elements in the 3′ region of AID mRNA, Teng et al. designed constructs containing a reporter linked either to a functional AID locus or to one in which the miR-155 elements had been mutated. In the latter case, loss of the ability to respond to miR-155 led to increases in AID expression and class-switch recombination in stimulated B cells. In contrast, somatic hypermutation was unaffected, although affinity maturation was unexpectedly impaired. Dorsett et al. noted similar effects of mutations in the AID mRNAmiR-155 binding site, which again corresponded with increased AID levels. A higher rate of AID-associated chromosomal translocations was also detected, suggesting that beyond its influence on normal B cell functions, this microRNA helps minimize potential oncogenic events. — SJS

Immunity 28, 621; 630 (2008).

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