Dorsett Yair, McBride Kevin M, Jankovic Mila, Gazumyan Anna, Thai To-Ha, Robbiani Davide F, Di Virgilio Michela, Reina San-Martin Bernardo, Heidkamp Gordon, Schwickert Tanja A, Eisenreich Thomas, Rajewsky Klaus, Nussenzweig Michel C
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Immunity. 2008 May;28(5):630-8. doi: 10.1016/j.immuni.2008.04.002. Epub 2008 May 1.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate vast networks of genes that share miRNA target sequences. To examine the physiologic effects of an individual miRNA-mRNA interaction in vivo, we generated mice that carry a mutation in the putative microRNA-155 (miR-155) binding site in the 3'-untranslated region of activation-induced cytidine deaminase (AID), designated Aicda(155) mice. AID is required for immunoglobulin gene diversification in B lymphocytes, but it also promotes chromosomal translocations. Aicda(155) caused an increase in steady-state Aicda mRNA and protein amounts by increasing the half-life of the mRNA, resulting in a high degree of Myc-Igh translocations. A similar but more pronounced translocation phenotype was also found in miR-155-deficient mice. Our experiments indicate that miR-155 can act as a tumor suppressor by reducing potentially oncogenic translocations generated by AID.
微小RNA（miRNA）是一类小的非编码RNA，可调控共享miRNA靶序列的大量基因网络。为了在体内研究单个miRNA与mRNA相互作用的生理效应，我们构建了在激活诱导的胞苷脱氨酶（AID）3'非翻译区的假定微小RNA-155（miR-155）结合位点携带突变的小鼠，命名为Aicda(155)小鼠。AID是B淋巴细胞中免疫球蛋白基因多样化所必需的，但它也会促进染色体易位。Aicda(155)通过增加mRNA的半衰期导致稳态Aicda mRNA和蛋白量增加，从而导致高度的Myc-Igh易位。在miR-155缺陷小鼠中也发现了类似但更明显的易位表型。我们的实验表明，miR-155可通过减少由AID产生的潜在致癌易位而发挥肿瘤抑制作用。
