mRNA decay (Kramer lab)
Trypanosomes use an ApaH-like phosphatase for mRNAs decapping
mRNA decapping is the critical step in 5’-3’ mRNA decay. Usually, a nudix domain protein (the prototype is Dcp2) hydrolyses the phosphate bound of the mRNA cap between the alpha and beta phosphate and produces monophosphorylated RNAs, which become a substrate for an exoribonuclease. Trypanosomes have a highly unusual cap structure that is heavily methylated at the first four transcribed nucleotides (cap4). This could be the reason why they do not have a homologue to Dcp2. Instead, we recently round that the parasites use an ApaH-like phosphatase as their major decapping enzyme. The further characterisation of this enzyme is a core focus of the Kramer lab. ALPH1 is the first non-nudix- domain decapping enzyme and it is already clear that the decapping mechanism is very different: cleavage does not take place between the alpha and beta phosphate. Furthermore, ApaH-like phosphatases, which originate from bacteria, are present in a patchy way throughout all the eukaryotic super-groups, but no enzyme has yet been functionally characterised. It is very tempting to speculate that ApaH like phosphatases also act in mRNA decapping in other eukaryotes.
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