Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism

Mikalai Malinouski, Nesrin M. Hasan, Yan Zhang, Javier Seravalli, Jie Lin, Andrei Avanesov, Svetlana Lutsenko, Vadim N. Gladyshev

Research output: Contribution to journalArticle

Abstract

Trace elements are essential for human metabolism and dysregulation of their homoeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and post-translational modifications; and the iron levels are influenced by iron import and expression of the iron/haeme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated data set opens new directions for studies of human trace element metabolism.

Original languageEnglish (US)
Article number3301
JournalNature Communications
Volume5
DOIs
StatePublished - Feb 13 2014

Fingerprint

genome
Trace Elements
metabolism
RNA Interference
Metabolism
trace elements
genes
Genes
Genome
Iron
machinery
iron
Machinery
lipid metabolism
Selenoproteins
Selenocysteine
homeostasis
regulators
Protein Transport
Post Translational Protein Processing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Malinouski, M., Hasan, N. M., Zhang, Y., Seravalli, J., Lin, J., Avanesov, A., ... Gladyshev, V. N. (2014). Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism. Nature Communications, 5, [3301]. https://doi.org/10.1038/ncomms4301

Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism. / Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

In: Nature Communications, Vol. 5, 3301, 13.02.2014.

Research output: Contribution to journalArticle

Malinouski, M, Hasan, NM, Zhang, Y, Seravalli, J, Lin, J, Avanesov, A, Lutsenko, S & Gladyshev, VN 2014, 'Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism', Nature Communications, vol. 5, 3301. https://doi.org/10.1038/ncomms4301
Malinouski, Mikalai ; Hasan, Nesrin M. ; Zhang, Yan ; Seravalli, Javier ; Lin, Jie ; Avanesov, Andrei ; Lutsenko, Svetlana ; Gladyshev, Vadim N. / Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism. In: Nature Communications. 2014 ; Vol. 5.
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