Post-transcriptional control of lymphocyte development
Non-coding (nc)RNAs, such as microRNAs have emerged as a novel layer of post-transcriptional gene regulation. Our laboratory is interest how a progenitor cell’s decision to become a T cell or another lymphoid or non-lymphoid cell type is controlled by ncRNA. To this end, we have conducted microRNA gene expression screens at lineage decision checkpoints and we have begun to establish regulatory networks comprising both, microRNAs and transcriptional regulators. In order to assess the function of microRNAs identified in these screens in vivo we employ classical gene targeting as well as CRISPR/Cas9-mediated deletion. We have shown that deletion of microRNA miR-181a/b-1 causes a profound defect in the generation of unconventional T cells. Furthermore, we have recently demonstrated that a cluster of microRNAs, miR-17~92 also termed (oncomiR-1 because of its function as an oncogene), is critical for early T-cell development. Ultimately, our experiments aim at integrating post-transcriptional gene regulation in a broader gene regulatory context. Understanding post-transcriptional gene regulatory programs will help to better understand molecular mechanisms of tumor formation and may result in the identification of novel therapeutic targets.
Key publications:
Krueger A, Łyszkiewicz M, Heissmeyer V (2022). Post-transcriptional control of T-cell development in the thymus. Immunol Lett 247:1-12.
Grewers Z, Krueger A (2020). MicroRNA miR-181 - A Rheostat for TCR Signaling in Thymic Selection and Peripheral T-Cell Function. Int J Mol Sci. 21(17):6200.
Łyszkiewicz M, Winter SJ, Witzlau K, Föhse L, Brownlie R, Puchałka J, Verheyden NA, Kunze-Schumacher H, Imelmann E, Blume J, Raha S, Sekiya T, Yoshimura A, Frueh JT, Ullrich E, Huehn J, Weiss S, Gutierrez MG, Prinz I, Zamoyska R, Ziętara N*, Krueger A* (2019). miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity. PLoS Biol 17(3):e2006716. * Equal contribution.
Winter SJ, Kunze-Schumacher H, Imelmann I, Grewers Z, Osthues T, Krueger A (2019). MicroRNA miR-181a/b-1 controls MAIT cell development. Immunol Cell Biol. 97(2):190-202.
Ziętara N, Łyszkiewicz M, Witzlau K, Naumann R, Hurwitz R, Langemeier J, Bohne J, Sandrock I, Ballmaier M, Weiss S, Prinz I*, and Krueger A* (2013). Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells. Proc. Natl. Acad. Sci. USA 110:7407-7412. * Equal contribution.