Initially considered as “junk” DNA, it is now clear that the non-protein coding part of the human genome, which comprises about 98 % of the ~3·109 DNA bases, is extensively transcribed and gives rise to numerous non-coding RNAs. In our group, we are mainly interested in deciphering the role of these RNAs in hematopoiesis and immune function. At the moment, we are focusing on two different types of non-coding RNAs, microRNAs (miRNAs) and long intergenic non-coding RNAs (lincRNAs).
MiRNAs are small, non-coding RNAs that mediate posttranscriptional silencing of a predicted 60% of protein-coding genes in mammals. In our work, we are trying to decipher how microRNAs influence
early B lymphocyte development and, if aberrantly expressed, promote cellular transformation.
LincRNAs form a heterogeneous group of long non-coding RNAs transcribed from independent genomic units that do not overlap with any coding genes. With few exceptions, we are far from understanding which of the thousands of lincRNAs expressed in each cell confers a regulatory function, and if so, how their function is mediated on the molecular level.
To unravel the role of individual lincRNAs in hematopoiesis and the immune system, we combine CRISPR/Cas9-mediated loss-of-function with a broad panel of molecular and biochemical approaches.
A novel mechanism we have called "cluster assistance" describes how suboptimal primary miRNA stem-loops can be processed when paired with another standard miRNA
hairpin on the same transcript.
Hutter K, Lohmüller M, Jukic A, Eichin F, Avci S, Labi V, Szabo TG, Hoser SM, Hüttenhofer A, Villunger A, Herzog S. Mol Cell. 2020 Jun 4;78(5):876-889.e6. doi: 10.1016/j.molcel.2020.05.011. PMID: 32502422
Pre-B cells induce miR-15 family members in an IL-7-dependent manner to stop proliferation and induce differentiation into immature B cells.