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Univ.-Prof. Dr. med. Roman Müller
Department II of Internal Medicine University Hospital Cologne
Kerpener Str. 62
50937 Cologne, Germany
+49 221 478-30627
roman-ulrich.mueller@uk-koeln.de

Prof. Dr. Christoph Dieterich
Section of Bioinformatics and Systems Cardiology Department of Internal Medicine III
University Hospital Heidelberg
Im Neuenheimer Feld 669
69120 Heidelberg, Germany
+49 6221 56-36884
christoph.dieterich@med.uni-heidelberg.de

Institution
University Hospital of Cologne
Nephrolab Cologne
CECAD Research Center
Joseph-Stelzmann-Str. 26
50931 Cologne, Germany

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Christoph Dieterich, Roman U. Müller

Podocyte lncRNAs: novel players in FSGS

Non-coding RNAs have been linked to various diseases including focal segmental glomerulosclerosis (FSGS). The revolution in sequencing technology has opened up entirely new opportunities regarding the discovery of novel transcripts. It is now widely agreed that around 80% of the human genome is transcribed in a cell-type and context-specific manner. The vast majority of all transcripts lacks any protein coding potential. Among these non-coding transcripts, the novel class of long non-coding RNAs (lncRNAs) has gained major attention due to an increasing number of studies showing its importance in organ development and disease. However, how this occurs on the molecular level and how lncRNAs impact on organ function and disease has – albeit few exceptions – remained elusive with virtually no data at all regarding FSGS. We are studying the role of lncRNAs in FSGS to exploit the great potential of this emerging field for identifying novel diagnostic and therapeutic targets. In the first funding period of CRU329, we have established a pipeline that identifies conserved podocyte lncRNAs that are dysregulated in FSGS (https://calinca.dieterichlab.org/). This pipeline is now the basis to currently performed analyses of the functional implications of these lncRNAs in the pathogenesis of FSGS.

PROJECT RELATED PUBLICATIONS

Bartram, M.P., Amendola, E., Benzing, T., Schermer, B., de Vita, G. and Müller, R.-U., 2016. Mice lacking microRNAs in Pax8-expressing cells develop hypothyroidism and end-stage renal failure. BMC Mol. Biol. 17, 11. doi:10.1186/s12867-016-0064-x

Bartram, M.P., Dafinger, C., Habbig, S., Benzing, T., Schermer, B. and Müller, R.-U., 2015. Loss of Dgcr8-mediated microRNA expression in the kidney results in hydronephrosis and renal malformation. BMC Nephrol 16, 55. doi:10.1186/s12882-015-0053-1

Krebs, C.F., Kapffer, S., Paust, H.-J., Schmidt, T., Bennstein, S.B., Peters, A., Stege, G., Brix, S.R., Meyer-Schwesinger, C., Müller, R.-U., Turner, J.-E., Steinmetz, O.M., Wolf, G., Stahl, R.A.K. and Panzer, U., 2013. Micro-RNA-155 Drives TH17 Immune Response and Tissue Injury in Experimental Crescentic GN. J. Am. Soc. Nephrol. doi:10.1681/ASN.2013020130

Beyer, M., Thabet, Y., Müller, R.-U., Sadlon, T., Classen, S., Lahl, K., Basu, S., Zhou, X., Bailey-Bucktrout, S.L., Krebs, W., Schönfeld, E.A., Böttcher, J., Golovina, T., Mayer, C.T., Hofmann, A., Sommer, D., Debey-Pascher, S., Endl, E., Limmer, A., Hippen, K.L., Blazar, B.R., Balderas, R., Quast, T., Waha, A., Mayer, G., Famulok, M., Knolle, P.A., Wickenhauser, C., Kolanus, W., Schermer, B., Bluestone, J.A., Barry, S.C., Sparwasser, T., Riley, J.L. and Schultze, J.L., 2011. Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation. Nature Immunology 12, 898–907. doi:10.1038/ni.2084

Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A.O., Landthaler, M., Lin, C., Socci, N.D., Hermida, L., Fulci, V., Chiaretti, S., Foà, R., Schliwka, J., Fuchs, U., Novosel, A., Müller, R.-U., Schermer, B., Bissels, U., Inman, J., Phan, Q., Chien, M., Weir, D.B., Choksi, R., De Vita, G., Frezzetti, D., Trompeter, H.-I., Hornung, V., Teng, G., Hartmann, G., Palkovits, M., Di Lauro, R., Wernet, P., Macino, G., Rogler, C.E., Nagle, J.W., Ju, J., Papavasiliou, F.N., Benzing, T., Lichter, P., Tam, W., Brownstein, M.J., Bosio, A., Borkhardt, A., Russo, J.J., Sander, C., Zavolan, M. and Tuschl, T., 2007. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401–1414. doi:10.1016/j.cell.2007.04.040

Rajman, M., Metge, F., Fiore, R., Khudayberdiev, S., Aksoy-Aksel, A., Bicker, S., Ruedell Reschke, C., Raoof, R., Brennan, G.P., Delanty, N., Farrell, M.A., O’Brien, D.F., Bauer, S., Norwood, B., Veno, M.T., Krüger, M., Braun, T., Kjems, J., Rosenow, F., Henshall, D.C., Dieterich, C. and Schratt, G., 2017. A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses. EMBO J. 36, 1770–1787. doi:10.15252/embj.201695748

Blin, K., Dieterich, C., Wurmus, R., Rajewsky, N., Landthaler, M. and Akalin, A., 2015. DoRiNA 2.0--upgrading the doRiNA database of RNA interactions in post-transcriptional regulation. Nucleic Acids Res. 43, D160-167. doi:10.1093/nar/gku1180

Cheng, J., Metge, F. and Dieterich, C., 2015. Specific identification and quantification of circular RNAs from sequencing data. Bioinformatics. doi:10.1093/bioinformatics/btv656

Ivanov, A., Memczak, S., Wyler, E., Torti, F., Porath, H.T., Orejuela, M.R., Piechotta, M., Levanon, E.Y., Landthaler, M., Dieterich, C. andRajewsky, N., 2015. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10, 170–177. doi:10.1016/j.celrep.2014.12.019

Valluy, J., Bicker, S., Aksoy-Aksel, A., Lackinger, M., Sumer, S., Fiore, R., Wüst, T., Seffer, D., Metge, F., Dieterich, C., Wöhr, M., Schwarting, R. and Schratt, G., 2015. A coding-independent function of an alternative Ube3a transcript during neuronal development. Nat. Neurosci. 18, 666–673. doi:10.1038/nn.3996