Open AccessAn autonomous metabolic role for Spen
Author(s) -
Kelsey Hazegh,
Travis Nemkov,
Angelo D’Alessandro,
John D. Diller,
Jenifer Monks,
James L. McManaman,
Kenneth L. Jones,
Kirk C. Hansen,
Tânia Reis
Publication year - 2017
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1006859
Subject(s) - biology , context (archaeology) , catabolism , microbiology and biotechnology , regulator , function (biology) , phenotype , transcription factor , regulation of gene expression , gene , metabolism , genetics , biochemistry , paleontology
Preventing obesity requires a precise balance between deposition into and mobilization from fat stores, but regulatory mechanisms are incompletely understood. Drosophila Split ends (Spen) is the founding member of a conserved family of RNA-binding proteins involved in transcriptional regulation and frequently mutated in human cancers. We find that manipulating Spen expression alters larval fat levels in a cell-autonomous manner. Spen-depleted larvae had defects in energy liberation from stores, including starvation sensitivity and major changes in the levels of metabolic enzymes and metabolites, particularly those involved in β-oxidation. Spenito, a small Spen family member, counteracted Spen function in fat regulation. Finally, mouse Spen and Spenito transcript levels scaled directly with body fat in vivo , suggesting a conserved role in fat liberation and catabolism. This study demonstrates that Spen is a key regulator of energy balance and provides a molecular context to understand the metabolic defects that arise from Spen dysfunction.