RcLS2F – A Novel Fungal Class 1 KDAC Co-repressor Complex in Aspergillus nidulans

Abstract

The fungal class 1 lysine deacetylase (KDAC) RpdA is a promising target for prevention and treatment of invasive fungal infection. RpdA is essential for survival of the most common airborne mold pathogen Aspergillus fumigatus and the model organism Aspergillus nidulans. In A. nidulans, RpdA depletion induced production of previously unknown small bioactive substances. As known from yeasts and mammals, class 1 KDACs act as components of multimeric protein complexes, which previously was indicated also for A. nidulans. Composition of these complexes, however, remained obscure. In this study, we used tandem affinity purification to characterize different RpdA complexes and their composition in A. nidulans. In addition to known class 1 KDAC interactors, we identified a novel RpdA complex, which was termed RcLS2F. It contains ScrC, previously described as suppressor of the transcription factor CrzA, as well as the uncharacterized protein FscA. We show that recruitment of FscA depends on ScrC and we provide clear evidence that crzA suppression by ScrC depletion is due to a lack of transcriptional repression caused by loss of the novel RcLS2F complex. Moreover, RcLS2F is essential for sexual development and engaged in an autoregulatory feedback loop.

Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds

“…The members of the Set3C corresponding TIG1 complex from M. oryzae have also been implicated in virulence [63]. Although Hos2 and Hda1 have been shown to be part of an Rpd3L expanded complex in S. cerevisiae and S. pombe [66], the Aspergillus nidulans Hos2 ortholog HosA was never identified by tandem affinity purifications (TAPs) with RpdA as bait [67]. RpdA TAP in A. nidulans, however, led to the identification of a new complex termed RcLS2F [67].…”

“…Although Hos2 and Hda1 have been shown to be part of an Rpd3L expanded complex in S. cerevisiae and S. pombe [66], the Aspergillus nidulans Hos2 ortholog HosA was never identified by tandem affinity purifications (TAPs) with RpdA as bait [67]. RpdA TAP in A. nidulans, however, led to the identification of a new complex termed RcLS2F [67]. The RcLS2F complex represses genes in a KDAC activity-dependent manner and is essential for sexual reproduction [67].…”

“…RpdA TAP in A. nidulans, however, led to the identification of a new complex termed RcLS2F [67]. The RcLS2F complex represses genes in a KDAC activity-dependent manner and is essential for sexual reproduction [67]. This complex consists of the conserved Sin3-Ume1/Prw1/Rpd3 core that is also part of the RpdAL and RpdAS complexes, which have counterparts in S. cerevisiae and S. pombe as well [67].…”

“…The RcLS2F complex represses genes in a KDAC activity-dependent manner and is essential for sexual reproduction [67]. This complex consists of the conserved Sin3-Ume1/Prw1/Rpd3 core that is also part of the RpdAL and RpdAS complexes, which have counterparts in S. cerevisiae and S. pombe as well [67]. The defining members are ScrC and FscA; the former has already been described as extragenic suppressor of crzA [68].…”

BcRPD3-Mediated Histone Deacetylation Is Involved in Growth and Pathogenicity of Botrytis cinerea

“…Previous reports have shown that class I HDACs function as members of protein complexes in vitro . For example, in filamentous fungi, RpdA interacted with RcLS2F in A. nidulans ( Bauer et al, 2020 ). Rpd3L-like HDAC complex in Fusarium Pseudograminearum contained multiple partners including FpDep1, FpSds3, FpSin3, FpRpd3, FpRxt3, FpCti6, FpPho23, and FpUme6 ( Zhang et al, 2020 ).…”