Differential roles of two DDX17 isoforms in the formation of membraneless organelles

Yuya Hirai1, Eisuke Domae2, Yoshihiro Yoshikawa2

  • 1Department of Biology, Osaka Dental University, 8-1, Kuzuha Hanazono-cho, Hirakata, Osaka 573-1121, Japan.

Journal of Biochemistry
|February 18, 2020
PubMed

Insights

The DEAD-box RNA helicase DDX17 has two isoforms, p72 and p82. Intrinsically disordered regions (IDRs) in p82 influence its localization and membraneless organelle formation, highlighting the role of protein structure and activity in cellular organization.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DDX17 is an RNA helicase belonging to the DEAD-box protein family.
  • DDX17 exists in two isoforms: p72 and p82.
  • The p82 isoform contains intrinsically disordered regions (IDRs) linked to membraneless organelle (MLO) formation.

Purpose of the Study:

  • To investigate the differential localization and dynamics of DDX17 isoforms.
  • To explore the role of intrinsically disordered regions (IDRs) and enzymatic activity in DDX17 function.
  • To understand the contribution of DDX17 to membraneless organelle (MLO) formation.

Main Methods:

  • Immunofluorescence microscopy to determine protein localization.
  • Fluorescence recovery after photobleaching (FRAP) to assess intranuclear mobility.
  • Analysis of enzymatic mutants to study function.

Main Results:

  • p72 primarily localizes to the nucleoplasm, while p82 is found in both nucleoplasm and nucleoli.
  • p82 exhibits slower intranuclear mobility compared to p72.
  • Enzymatic mutants of both isoforms accumulate in stress granules, and p82 mutants lose nucleolar localization.

Conclusions:

  • Intrinsically disordered regions (IDRs) and enzymatic activity are crucial for the intracellular distribution of DDX17.
  • These factors play a significant role in the formation and regulation of membraneless organelles (MLOs).
  • Differential localization and dynamics of DDX17 isoforms are key to their distinct cellular roles.

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