TDP-43 identified from a genome wide RNAi screen for SOD1 regulators

Balajee R. Somalinga, Cameron E. Day, Shuguang Wei, Michael G. Roth, Philip J. Thomas

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a late-onset, progressive neurodegenerative disease affecting motor neurons in the brain stem and spinal cord leading to loss of voluntary muscular function and ultimately, death due to respiratory failure. A subset of ALS cases are familial and associated with mutations in superoxide dismutase 1 (SOD1) that destabilize the protein and predispose it to aggregation. In spite of the fact that sporadic and familial forms of ALS share many common patho-physiological features, the mechanistic relationship between SOD1-associated and sporadic forms of the disease if any, is not well understood. To better understand any molecular connections, a cell-based protein folding assay was employed to screen a whole genome RNAi library for genes that regulate levels of soluble SOD1. Statistically significant hits that modulate SOD1 levels, when analyzed by pathway analysis revealed a highly ranked network containing TAR DNA binging protein (TDP-43), a major component of aggregates characteristic of sporadic ALS. Biochemical experiments confirmed the action of TDP-43 on SOD1. These results highlight an unexpected relationship between TDP-43 and SOD1 which may have implications in disease pathogenesis.

Original languageEnglish (US)
Article numbere35818
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 26 2012

Fingerprint

RNA Interference
Superoxide Dismutase
superoxide dismutase
Genes
Genome
genome
Neurodegenerative diseases
Protein folding
binging
protein folding
Genomic Library
DNA libraries
Protein Folding
Amyotrophic Lateral Sclerosis
neurodegenerative diseases
Motor Neurons
protein aggregates
brain stem
motor neurons
Gene Library

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

TDP-43 identified from a genome wide RNAi screen for SOD1 regulators. / Somalinga, Balajee R.; Day, Cameron E.; Wei, Shuguang; Roth, Michael G.; Thomas, Philip J.

In: PLoS One, Vol. 7, No. 4, e35818, 26.04.2012.

Research output: Contribution to journalArticle

Somalinga, Balajee R. ; Day, Cameron E. ; Wei, Shuguang ; Roth, Michael G. ; Thomas, Philip J. / TDP-43 identified from a genome wide RNAi screen for SOD1 regulators. In: PLoS One. 2012 ; Vol. 7, No. 4.
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