Drosophila TRF2 and TAF9 regulate lipid droplet size and phospholipid fatty acid composition

PLoS Genet. 2017 Mar 8;13(3):e1006664. doi: 10.1371/journal.pgen.1006664. eCollection 2017 Mar.

Abstract

The general transcription factor TBP (TATA-box binding protein) and its associated factors (TAFs) together form the TFIID complex, which directs transcription initiation. Through RNAi and mutant analysis, we identified a specific TBP family protein, TRF2, and a set of TAFs that regulate lipid droplet (LD) size in the Drosophila larval fat body. Among the three Drosophila TBP genes, trf2, tbp and trf1, only loss of function of trf2 results in increased LD size. Moreover, TRF2 and TAF9 regulate fatty acid composition of several classes of phospholipids. Through RNA profiling, we found that TRF2 and TAF9 affects the transcription of a common set of genes, including peroxisomal fatty acid β-oxidation-related genes that affect phospholipid fatty acid composition. We also found that knockdown of several TRF2 and TAF9 target genes results in large LDs, a phenotype which is similar to that of trf2 mutants. Together, these findings provide new insights into the specific role of the general transcription machinery in lipid homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Motifs
  • Animals
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism*
  • Fatty Acids / chemistry*
  • Homeostasis
  • Lipids / chemistry*
  • Mutation
  • Oxygen / chemistry
  • Peroxisomes / chemistry
  • Phenotype
  • Phospholipids / chemistry
  • RNA Interference
  • Sequence Analysis, RNA
  • TATA-Binding Protein Associated Factors / metabolism*
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Transcription Factor TFIID / chemistry
  • Transcription Factor TFIID / metabolism*

Substances

  • Drosophila Proteins
  • Fatty Acids
  • Lipids
  • Phospholipids
  • TATA-Binding Protein Associated Factors
  • TRF2 protein, Drosophila
  • Telomeric Repeat Binding Protein 2
  • Transcription Factor TFIID
  • e(y)1 protein, Drosophila
  • Oxygen

Grants and funding

Research reported here was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030300/0400), the National Basic Research Program of China (2013CB530606 and 2016YFA0500100) and the National Natural Science Foundation of China (11422108, 31325018, 31571377 and 31630019). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.