KAEA (SUDPRO), a member of the ubiquitous KEOPS/EKC protein complex, regulates the arginine catabolic pathway and the expression of several other genes in Aspergillus nidulans

Abstract

The kaeA(KAE1) (suDpro) gene, which was identified in Aspergillus nidulans as a suppressor of proline auxotrophic mutations, encodes the orthologue of Saccharomyces cerevisiae Kae1p, a member of the evolutionarily conserved KEOPS/EKC (Kinase, Endopeptidase and Other Proteins of Small size/Endopeptidase-like and Kinase associated to transcribed Chromatin) complex. In yeast, this complex has been shown to be involved in tRNA modification, transcription, and genome maintenance. In A. nidulans, mutations in kaeA result in several phenotypic effects, the derepression of arginine catabolism genes, and changes in the expression levels of several others, including genes involved in amino acid and siderophore metabolism, sulfate transport, carbon/energy metabolism, translation, and transcription regulation, such as rcoA(TUP1), which encodes the global transcriptional corepressor.

tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy

“…Although S. cerevisiae kae1Δ strains are viable, they have severe growth defects and pleiotropic phenotypes 4,18 and this is also the case in another fungus, Aspergillus nidulans. 36 In the human malaria parasite Plasmodium falciparum, the cytoplasmic KAE1 gene appears to be essential. 37 Recent studies have shown that the absence of KAE1 also leads to strong phenotypes in multicellular organisms, such tissue-specific cell growth regulated by t 6 A in flies.…”

Nuclear Functions of KaeA, a Subunit of the KEOPS Complex in Aspergillus nidulans

“…In the model filamentous fungus Aspergillus nidulans , mutations in the kaeA gene (previously called suDpro ) were identified as suppressors of proline auxotrophic ( pro − ) mutations [ 20 ]. Two characterized kaeA mutations (previously called suD19pro and suD25pro ) result in upregulation of agaA and otaA genes, coding for arginine catabolic enzymes: arginase and ornithine aminotransferase, respectively [ 21 , 22 ]. Both of these mutations are short deletions in the kaeA coding region, which do not change the reading frame.…”

“…These mutations do not change the sequence of the conserved regions of the protein. A model of the KaeA structure shows that amino acids from both deleted regions are localized on the protein surface, and it has been proposed that these deletions influence the interaction of KaeA with KEOPS subunits or other proteins [ 22 ].…”

“…Our previous results supported the hypothesis that in addition to its conserved role in tRNA modification, KaeA might be involved in transcription regulation. We postulated that the expression of some genes, e.g., arginine catabolism genes, might be directly regulated at the transcription level by KaeA, although, most probably, several observed pleiotropic effects of kaeA19/kaeA25 mutations were indirect [ 22 ].…”

Az opportunista humánpatogén Candida parapsilosis patomechanizmusának molekuláris szabályozottsága

“…Egy új tanulmány szerint, A. nidulans-ban a KEOPS/EKC komplex egyik tagja több olyan különböző metabolikus útvonal szabályozásában is részt vesz (Dzikowska és mtsi., 2015), amely útvonalak Candida fajokban összefüggésbe hozhatóak a patogenitás kialakulásával. Ezért a komplex egyes tagjai bizonyos fajok fertőzőképességét is befolyásolhatják.…”