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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Brady, Brenna L. Bassing, Craig H. Rupp, Levi J. |
| Description | Country affiliation: United States Author Affiliation: Brady BL ( Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA) |
| Abstract | The Dicer nuclease generates small RNAs that regulate diverse biological processes through posttranscriptional gene repression and epigenetic silencing of transcription and recombination. Dicer-deficient cells exhibit impaired differentiation, activity, proliferation, and survival. Dicer inactivation in developing mouse lymphocytes impairs their proliferation and survival and alters Ag receptor gene repertoires for largely undefined reasons. To elucidate functions of Dicer in lymphocyte development and Ag receptor locus transcription and recombination, we analyzed mice with conditional Dicer deletion in thymocytes containing unrearranged or prerearranged TCRß loci. Expression of either a preassembled functional TCRß gene (Vß1(NT)) or the prosurvival BCL2 protein inhibited death and partially rescued proliferative expansion of Dicer-deficient thymocytes. Notably, combined expression of Vß1(NT) and BCL2 completely rescued proliferative expansion of Dicer-deficient thymocytes and revealed that Dicer promotes survival of cells attempting TCRß recombination. Finally, inclusion of an endogenous preassembled DJß complex that enhances Vß recombination increased death and impaired proliferative expansion of Dicer-deficient thymocytes. These data demonstrate a critical role for Dicer in promoting survival of thymocytes experiencing DNA double-strand breaks (DSBs) during TCRß recombination. Because DSBs are common and ubiquitous in cells, our findings indicate that impaired cellular survival in response to DSBs should be considered when interpreting Dicer-deficient phenotypes. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1200957 |
| Journal | The Journal of Immunology |
| Issue Number | 7 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Dna Breaks, Double-stranded Ribonuclease Iii Metabolism Thymocytes Animals Cell Survival Genetics Mice Mice, Knockout Receptors, Antigen, T-cell, Alpha-beta Recombination, Genetic Immunology Research Support, N.i.h., Extramural Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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