Welcome to the Stoecklin Lab!

Posttransciptional Control of Gene Expression

Many genes are regulated at the posttranscriptional level by mechanisms that control the translation efficiency and degradation rate of the mRNA in the cytoplasm. Our main focus is a group of unstable mRNAs that contain AU-rich elements. We investigate how RNA-binding proteins regulate the stability of these mRNAs, and how their subcellular localization in processing bodies and stress granules affects translation and degradation rates. In addition, we search for tumors in which the regulation of mRNA stability is abnormal. Our principal model systems are macrophages and different mammalian cell lines. Specific topics of our research are:

-> Cis-acting elements: The AU-rich element (ARE) is the most abundant regulatory element found in unstable mRNAs of eukaryotic organisms. Using RNA-immunoprecipitation techniques followed by microarray analysis, we are exploring the spectrum of mRNAs regulated by AREs. In addition, we are identifying and characterizing novel classes of non-ARE destabilizing elements.
-> Trans-acting factors: A family of zinc-finger proteins including TTP is required for the degradation ARE-containing cytokine mRNAs in macrophages and T-cells. Upon extracellular stimulation, decay of these mRNAs is inhibited to allow for a rapid increase in cytokine production. Phosphorylation of TTP is important for stabilizing cytokine mRNAs, and current projects are aimed at further understanding how TTP activity is regulated.
-> Subcellular organization of mRNA decay: 5' to 3' degradation of mRNAs occurs in specific cytoplasmic foci termed processing bodies. In response to stress, most mRNAs are translationally repressed and aggregate in different cytoplasmic structures termed stress granules. We further explore how cells control the trafficking of mRNA between ribosomes, processing bodies and stress granules. DKFZ & ZMBH Alliance: Our lab is a Helmholtz Junior Research Group of the German Cancer Research Center (DKFZ). As members of the DKFZ & ZMBH Alliance, we are happy to have guest status at the ZMBH and thereby further the scientific and personal interactions between the two institutes. You may also visit our website at the DKFZ.

Selected Publications

Leppek K, Schott J, Reitter S, Poetz F, Hammond MC, Stoecklin G (2013) Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. Cell 153:869-81.

Hofmann S, Cherkasova V, Bankhead P, Bukau B, Stoecklin G (2012) Translation suppression promotes stress granule formation and cell survival in response to cold shock. Mol Biol Cell 23(19):3786-3800. Epub 2012 Aug 8.

Spasic M, Friedel CC, Schott J, Kreth J, Leppek K, Hofmnn S, Ozgur S, Stoecklin G (2012) Genome-wide assessment of AU-rich elements by the AREScore algorithm. PLoS Genet. 8(1):e1002433. doi 10.1271/journal.pgen.1002433. Epub 2012 Jan 5.

Sandler H, Kreth J, Timmers HT, Stoecklin G (2011) Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targetet for degradation by tristetraprolin. Nucleic Acids Res. 39(10):4373-86. Epub 2011 Jan 29.

Ozgur S Chekulaeva M, Stoecklin G (2010) Human Pat1b connects deadenylation with decapping and controls the assembly of processing bodies. Mol Cell Biol 30:4308-23.

Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WFC, Blackwell TK, Anderson P. (2004) MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay. EMBO J 23:1313-24.