The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease.
MicroRNAs (miRNAs) are implicated in the differentiation and function of many cell types. We provide genetic and in vivo evidence that the two RNaseIII enzymes, Drosha and Dicer, do indeed function in the same pathway. These have previously been shown to mediate the stepwise maturation of miRNAs (Lee, Y., C. Ahn, J. Han, H. Choi, J. Kim, J. Yim, J. Lee, P. Provost, O. Radmark, S. Kim, and V.N. Kim. 2003. Nature. 425:415-419), and genetic ablation of either within the T cell compartment, or specifically within Foxp3(+) regulatory T (T reg) cells, results in identical phenotypes. We found that miRNA biogenesis is indispensable for the function of T reg cells. Specific deletion of either Drosha or Dicer phenocopies mice lacking a functional Foxp3 gene or Foxp3(+) cells, whereas deletion throughout the T cell compartment also results in spontaneous inflammatory disease, but later in life. Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity.
Chong
Mark M W
MM
The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Rasmussen
Jeffrey P
JP
Rudensky
Alexander Y
AY
Rundensky
Alexander Y
AY
Littman
Dan R
DR
D000818:Animals; D002469:Cell Separation; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D010641:Phenotype; D043244:Ribonuclease III / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; C513400:Drosha protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases