ATP-independent diffusion of double-stranded RNA binding proteins

Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):151-6. doi: 10.1073/pnas.1212917110. Epub 2012 Dec 18.

Abstract

The proteins harboring double-stranded RNA binding domains (dsRBDs) play diverse functional roles such as RNA localization, splicing, editing, export, and translation, yet mechanistic basis and functional significance of dsRBDs remain unclear. To unravel this enigma, we investigated transactivation response RNA binding protein (TRBP) consisting of three dsRBDs, which functions in HIV replication, protein kinase R(PKR)-mediated immune response, and RNA silencing. Here we report an ATP-independent diffusion activity of TRBP exclusively on dsRNA in a length-dependent manner. The first two dsRBDs of TRBP are essential for diffusion, whereas the third dsRBD is dispensable. Two homologs of TRBP, PKR activator and R3D1-L, displayed the same diffusion, implying a universality of the diffusion activity among this protein family. Furthermore, a Dicer-TRBP complex on dsRNA exhibited dynamic diffusion, which was correlated with Dicer's catalytic activity. These results implicate the dsRNA-specific diffusion activity of TRBP that contributes to enhancing siRNA and miRNA processing by Dicer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Diffusion
  • Drosophila Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Fluorescence Resonance Energy Transfer
  • HeLa Cells
  • Humans
  • Microscopy, Fluorescence
  • Multiprotein Complexes / metabolism*
  • Oligonucleotides / genetics
  • Protein Structure, Tertiary / physiology
  • Protein Transport
  • RNA Interference
  • RNA, Double-Stranded / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / metabolism*

Substances

  • Drosophila Proteins
  • Loqs protein, Drosophila
  • Multiprotein Complexes
  • Oligonucleotides
  • PRKRA protein, human
  • RNA, Double-Stranded
  • RNA-Binding Proteins
  • trans-activation responsive RNA-binding protein
  • Adenosine Triphosphate
  • Ribonuclease III