Hentze Group

RNA-binding proteins in RNA biology and riboregulation

The Hentze group integrates a wide spectrum of systems-level, cell biological, molecular and biochemical approaches to study RNA-binding proteins (RBPs). We are especially interested in Riboregulation of RBPs and its importance in cell biology.


Previous and current research

Our research is focused on understanding principles of cellular function, especially in RNA Biology. RNA-binding proteins (RBPs) have been at the centre of our attention for more than three decades. We first discovered and defined RBPs as trans-acting regulatory factors in post-transcriptional gene regulation, especially in translational control and mRNA turnover. Work on e.g. the iron-responsive element (IRE)/iron regulatory protein (IRP) system in mammalian iron homeostasis (Hentze et al., Cell, 2004), on hnRNPs K and E1/2 in the translational control of lipoxygenase mRNA (Ostareck et al., Cell, 2001), and on Sex lethal in the translational regulation of msl-2 mRNA in Drosophila dosage compensation (Medenbach et al., Cell, 2011) has provided mechanistic insights into how RBPs regulate the cytoplasmic fate of mRNAs.

More recently, systematic, unbiased experimental approaches to RBP discovery, pioneered by our group, have more than doubled the number of identified RBPs (Castello et al, Cell, 2012), causing surprise, sparking debate, and opening doors to unexpected discoveries, especially that of riboregulation (Hentze et al., Nature Rev. Mol. Cell Biol., 2018) (Figure 1).

We define riboregulation as a regulatory principle by which any type of cellular RNA controls a biologically relevant function of a protein by direct, specific binding. While examples of this can be identified in publications from decades ago, we have proposed riboregulation as a general regulatory principle and suggest that it offers a new systematic paradigm of biological control. Key examples include the regulation of mammalian autophagy via p62 by vtRNA1-1 (Horos et al., Cell, 2019) and of mammalian glycolysis and stem cell differentiation by riboregulation of the glycolytic enzyme enolase-1 (Huppertz et al., Mol. Cell, 2022) (Figure 2).

Future projects and goals

The investigation of non-canonical RNA-binding proteins, especially of metabolic enzymes, and the role of riboregulation in the control of metabolism and cell differentiation forms the basis of our future scientific plans. We will continue our efforts towards the development of enabling methods and the implementation of necessary bioinformatic tools. Biological network control by riboregulation will be a focus of our future work. We plan

  • To investigate the importance of riboregulation for metabolic remodeling during stem cell differentiation
  • To decipher the mechanistic basis of riboregulation biochemically and structurally
  • To develop new therapeutic strategies targeting metabolic enzymes based on riboregulation
Figure 1: Riboregulation
Figure 2: p62 and ENO1 riboregulation