Dataset Information

Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

ABSTRACT: About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction-driven functional gene deorphanization.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase

SUBMITTER: Ulrich Goldmann

PROVIDER: MTBLS2205 | MetaboLights | 2021-03-29

REPOSITORIES: MetaboLights

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Publications

Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import.

Girardi Enrico E Agrimi Gennaro G Goldmann Ulrich U Fiume Giuseppe G Lindinger Sabrina S Sedlyarov Vitaly V Srndic Ismet I Gürtl Bettina B Agerer Benedikt B Kartnig Felix F Scarcia Pasquale P Di Noia Maria Antonietta MA Liñeiro Eva E Rebsamen Manuele M Wiedmer Tabea T Bergthaler Andreas A Palmieri Luigi L Superti-Furga Giulio G

Nature communications 20201201 1

About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and re ...[more]

PMID: 33262325

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Project description:All classes of RNA undergo processing. The two largest RNA processing complexes are those involved in rRNA biogenesis and mRNA splicing. Because of their complexity and essential roles, it has been difficult to dissect the functional interactions within these machines as well as to identify possible cross-talk with other steps in gene expression. Here we report the results of a high-density, quantitative genetic interaction map comprising 107,155 individual interactions involving 552 mutants, 166 of which are hypomorphic alleles of essential genes (This data is available at The Krogan Lab Interactome Database). Our data allow unique insights into the functional organization of the RNA processing machines. For example, we identify unexpected connections involving a component of the 19S proteasome, Sem1/Dss1. We show that Sem1 has genetic, physical and functional interactions with the mRNA export complex, Thp1-Sac3; it also interacts physically with a putative component of the COP9 signalosome, Csn12. We show using splicing-specific microarrays that Csn12 has an unanticipated role in mRNA splicing. Finally, we demonstrate the utility of this dataset in determining functions for uncharacterized ORFs. We show that deletion of the uncharacterized YNR004W causes a very similar splicing defect to that caused by deletion of TGS1, the enzyme that trimethylates the caps of snRNAs and snoRNAs. Keywords: E-MAP, RNA Processing, splicing, splicing-specific microarray, CSN12, COP9 signalosome Splicing-specific microarrays were used to assay the changes to splicing caused by deletion of several non-essential genes which had no previously characterized role in mRNA splicing but were suggested to be involved in this process by high-throughput genetic and/or protein-protein interaction data in Saccharomyces cerevisiae. The data includes samples collected from some mutants in log phase growth at 30 degrees C and from some mutants shifted to 16 degrees C, all competitively hybridized against wild type samples collected under the same conditions. .

Dataset Information

Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import

Publications

Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import.

Similar Datasets

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