A unique mRNA decapping complex in trypanosomes

Removal of the mRNA 5′ cap primes transcripts for degradation and is central for regulating gene ex-pression in ukaryotes. The canonical decapping en- zyme Dcp2 is stringently controlled by assembly into a dynamic multi-protein complex together with the 5′ -3′ exoribonuclease Xrn1. Kinetoplastida lack Dcp2 orthologues but instead rely on the ApaH-like phos-phatase ALPH1 for decapping. ALPH1 is composed of a catalytic domain flanked by C- and N-terminal extensions. We show that T. brucei ALPH1 is dimericin vitro and functions within a complex composed of the trypanosome Xrn1 ortholog XRNA and four pro-teins unique to Kinetoplastida, including two RNA-binding proteins and a CMGC-family protein kinase. All ALPH1-associated proteins share a unique and dynamic localization to a structure at the posterior pole of the cell, anterior to the microtubule plus ends. XRNA affinity capture in T. cruzi recapitulates this in-teraction network. The ALPH1 N-terminus is not re-quired for viability in culture, but essential for pos-terior pole localization. The C-terminus, in contrast, is required for localization to all RNA granule types, as well as for dimerization and interactions with XRNA and the CMGC kinase, suggesting possible regulatory mechanisms. Most significantly, the try-panosome decapping complex has a unique compo-sition, differentiating the process from opisthokonts.