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FUNCTIONAL GENOMICS

Caught in the genetic network: a novel regulator of lipid metabolism

Nature Metabolism volume 2, pages 483–484 (2020)Cite this article

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Genetic-interaction mapping and co-essentiality analyses in human cells reveal the orphan gene C12orf49 (also known as SPRING1) as a novel regulator of lipid-metabolism homeostasis.

Cellular metabolism is the result of the interplay of hundreds of intersecting pathways connecting small molecules, nutrients and metabolites with hundreds of enzymes and regulatory proteins1. This complex system allows for flexible yet robust metabolic responses to external changes. Assessing the contributions of single genes within this complex system remains a challenging process. The revolution in genetics that started through the gradual adoption of the CRISPR–Cas system by the scientific community has already borne thousands of studies in which the functions of individual genes have been investigated with unprecedented speed and precision, across many organisms. These studies primarily assessed one perturbation in one experimental system at a time: one gene, one scored phenotype. In this issue of Nature Metabolism, two studies by Aregger et al.2 and Bayraktar et al.3 highlight complementary strategies to overcome the issues of redundancy and complexity in cellular metabolism. These strategies have converged on the identification of a novel regulator of lipid metabolism. The approaches applied are important because they not only can establish functional relationships among genes but also have the potential to uncover many phenotypes that are ‘hidden’ by the high functional redundancy in eukaryotes. Both studies explore the effects of using these enhanced genetic approaches, which are conceptually comparable to having higher optical magnification in an imaging study, to examine human lipid-metabolism pathways.

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Fig. 1: The genetic interactions and co-essentiality networks of C12orf49 reflect its role in the SREBP pathway.

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Authors and Affiliations

  1. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria

    Enrico Girardi & Giulio Superti-Furga

  2. Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Giulio Superti-Furga

Authors
  1. Enrico Girardi
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  2. Giulio Superti-Furga
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Correspondence to Enrico Girardi or Giulio Superti-Furga.

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The authors declare no competing interests.

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Girardi, E., Superti-Furga, G. Caught in the genetic network: a novel regulator of lipid metabolism. Nat Metab 2, 483–484 (2020). https://doi.org/10.1038/s42255-020-0218-5

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