Title |
Non-mitochondrial aconitase regulates the expression of iron-uptake genes by controlling the RNA turnover process in fission yeast |
Author |
Soo-Yeon Cho1,2, Soo-Jin Jung2,3, Kyoung-Dong Kim1*, and Jung-Hye Roe2* |
Address |
1Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Republic of Korea, 2School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea, 3Center for RNA Research, Institute for Basic Science, Seoul 02841, Republic of Korea |
Bibliography |
Journal of Microbiology, 59(12),1075–1082, 2021,
|
DOI |
10.1007/s12275-021-1438-4
|
Key Words |
aconitase, iron homeostasis, iron-regulatory protein,
RNA degradation, fission yeast |
Abstract |
Aconitase, a highly conserved protein across all domains of
life, functions in converting citrate to isocitrate in the tricarboxylic
acid cycle. Cytosolic aconitase is also known to act as
an iron regulatory protein in mammals, binding to the RNA
hairpin structures known as iron-responsive elements within
the untranslated regions of specific RNAs. Aconitase-2 (Aco2)
in fission yeast is a fusion protein consisting of an aconitase
and a mitochondrial ribosomal protein, bL21, residing not
only in mitochondria but also in cytosol and the nucleus. To
investigate the role of Aco2 in the nucleus and cytoplasm of
fission yeast, we analyzed the transcriptome of aco2ΔN mutant
that is deleted of nuclear localization signal (NLS). RNA
sequencing revealed that the aco2ΔN mutation caused increase
in mRNAs encoding iron uptake transporters, such as
Str1, Str3, and Shu1. The half-lives of mRNAs for these genes
were found to be significantly longer in the aco2ΔN mutant
than the wild-type strain, suggesting the role of Aco2 in mRNA
turnover. The three conserved cysteines required for the catalytic
activity of aconitase were not necessary for this role.
The UV cross-linking RNA immunoprecipitation analysis
revealed that Aco2 directly bound to the mRNAs of iron uptake
transporters. Aco2-mediated degradation of iron-uptake
mRNAs appears to utilize exoribonuclease pathway that involves
Rrp6 as evidenced by genetic interactions. These results
reveal a novel role of non-mitochondrial aconitase protein
in the mRNA turnover in fission yeast to fine-tune iron
homeostasis, independent of regulation by transcriptional
repressor Fep1. |