Is mRNA decapping by ApaH like phosphatases present in eukaryotes beyond the Kinetoplastida?

Londoño, Paula Andrea Castañeda; Banholzer, Nicole; Bannermann, Bridget; Krämer, Susanne

doi:10.1186/s12862-021-01858-x

Cited by 3 publications

(1 citation statement)

References 72 publications

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“…These proteins perform an important cap quality control mechanism by selectively targeting incompletely capped mRNAs ( Jiao et al, 2010 ; Chang et al, 2012 ; Jiao et al, 2013 ), and also process NAD + , FAD + and dpCoA-capped mRNAs ( Jiao et al, 2017 ; Doamekpor et al, 2020 ). The ApaH-like phosphatase is the major decapping enzyme that degrades the unique Cap 4 in Trypanosoma ( Kramer, 2017 ), and does not seem to be functionally conserved outside of kinetoplastids ( Castaneda Londono et al, 2021 ).…”

Section: The Dcp1/2 Complex Is the Main Decapping Holo-enzyme In Euka...mentioning

confidence: 99%

Eukaryotic mRNA Decapping Activation

Vidya

2022

Front. Genet.

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The 5′-terminal cap is a fundamental determinant of eukaryotic gene expression which facilitates cap-dependent translation and protects mRNAs from exonucleolytic degradation. Enzyme-directed hydrolysis of the cap (decapping) decisively affects mRNA expression and turnover, and is a heavily regulated event. Following the identification of the decapping holoenzyme (Dcp1/2) over two decades ago, numerous studies revealed the complexity of decapping regulation across species and cell types. A conserved set of Dcp1/2-associated proteins, implicated in decapping activation and molecular scaffolding, were identified through genetic and molecular interaction studies, and yet their exact mechanisms of action are only emerging. In this review, we discuss the prevailing models on the roles and assembly of decapping co-factors, with considerations of conservation across species and comparison across physiological contexts. We next discuss the functional convergences of decapping machineries with other RNA-protein complexes in cytoplasmic P bodies and compare current views on their impact on mRNA stability and translation. Lastly, we review the current models of decapping activation and highlight important gaps in our current understanding.

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Section: The Dcp1/2 Complex Is the Main Decapping Holo-enzyme In Euka...mentioning

confidence: 99%

Eukaryotic mRNA Decapping Activation

Vidya

2022

Front. Genet.

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A unique mRNA decapping complex in trypanosomes

Kramer,

Karolak,

Odenwald

et al. 2023

Nucleic Acids Research

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Removal of the mRNA 5′ cap primes transcripts for degradation and is central for regulating gene expression in eukaryotes. The canonical decapping enzyme 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 phosphatase ALPH1 for decapping. ALPH1 is composed of a catalytic domain flanked by C- and N-terminal extensions. We show that T. brucei ALPH1 is dimeric in vitro and functions within a complex composed of the trypanosome Xrn1 ortholog XRNA and four proteins 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 interaction network. The ALPH1 N-terminus is not required for viability in culture, but essential for posterior 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 trypanosome decapping complex has a unique composition, differentiating the process from opisthokonts.

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The diadenosine tetraphosphate hydrolase ApaH contributes to Pseudomonas aeruginosa pathogenicity

Cervoni,

Sposato,

Ferri

et al. 2024

PLoS Pathog

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The opportunistic bacterial pathogen Pseudomonas aeruginosa causes a wide range of infections that are difficult to treat, largely because of the spread of antibiotic-resistant isolates. Antivirulence therapy, í.e. the use of drugs that inhibit the expression or activity of virulence factors, is currently considered an attractive strategy to reduce P. aeruginosa pathogenicity and complement antibiotic treatments. Because of the multifactorial nature of P. aeruginosa virulence and the broad arsenal of virulence factors this bacterium can produce, the regulatory networks that control the expression of multiple virulence traits have been extensively explored as potential targets for antivirulence drug development. The intracellular signaling molecule diadenosine tetraphosphate (Ap4A) has been reported to control stress resistance and virulence-related traits in some bacteria, but its role has not been investigated in P. aeruginosa so far. To fill this gap, we generated a mutant of the reference strain P. aeruginosa PAO1 that lacks the Ap4A-hydrolysing enzyme ApaH and, consequently, accumulates high intracellular levels of Ap4A. Phenotypic and transcriptomic analyses revealed that the lack of ApaH causes a drastic reduction in the expression of several virulence factors, including extracellular proteases, elastases, siderophores, and quorum sensing signal molecules. Accordingly, infection assays in plant and animal models demonstrated that ApaH-deficient cells are significantly impaired in infectivity and persistence in different hosts, including mice. Finally, deletion of apaH in P. aeruginosa clinical isolates demonstrated that the positive effect of ApaH on the production of virulence-related traits and on infectivity is conserved in P. aeruginosa. This study provides the first evidence that the Ap4A-hydrolysing enzyme ApaH is important for P. aeruginosa virulence, highlighting this protein as a novel potential target for antivirulence therapies against P. aeruginosa.

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Is mRNA decapping by ApaH like phosphatases present in eukaryotes beyond the Kinetoplastida?

Cited by 3 publications

References 72 publications

Eukaryotic mRNA Decapping Activation

Eukaryotic mRNA Decapping Activation

A unique mRNA decapping complex in trypanosomes

The diadenosine tetraphosphate hydrolase ApaH contributes to Pseudomonas aeruginosa pathogenicity

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