Postdoctoral Fellow

Meyerhofstraße 1
69117 Heidelberg

Telephone: +49 6221 387-8164

The moonlighting function of the TCA cycle enzymes

The tricarboxylic acid (TCA) cycle is one of the central pathways providing the cell with energy; it involves the intricate interplay of several enzymes. These essential enzymes have acquired additional functions through evolution, as in the case of aconitase (iron homeostasis) or succinate dehydrogenase (tumour suppression). Proteins with multiple functions are commonly referred to as ‘moonlighting proteins’. Recently, our laboratory identified that the majority of TCA cycle enzymes bind RNA in human cells. This observation leads to a series of research questions; which RNA molecules are bound, do different enzymes have the same set of bound targets and does the binding have a regulatory effect.

The planned experiments aim to uncover a new regulation pathway of the TCA cycle, which has so far been unrecognised. I will elucidate the way in which moonlighting proteins, which have gained the capacity to bind RNA, are active post-transcriptional regulators. In recent years, TCA cycle enzymes have been implicated in causing carcinogenesis, which has so far pointed towards metabolic alterations as the underlying hallmark of some forms of cancer. However, the fact that these enzymes can bind RNA might open up a new perspective on their role in carcinogenesis. Point mutations within the RNA binding pockets of these enzymes might alter the finely-balanced RNA and metabolite binding equilibrium and thereby disrupt cellular homeostasis.


Huppertz I., Attig J., D’Ambrogio A., Easton L.E., Sibley C.R., Sugimoto Y., Tajnik M., König J. and Ule J.(2014) iCLIP: Protein–RNA interactions at nucleotide resolution. Methods. Feb 2014; 65(3): 274–287.

Chan SL., Huppertz I., Yao C., Weng L., Moresco J.J., Yates J.R., Ule J., Manley J.L., and Shi Y. (2014) CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3’processing. Genes and Development. Oct 2014