An RNA-zipcode-independent mechanism that localizes Dia1 mRNA to the perinuclear ER through interactions between Dia1 nascent peptide and Rho-GTP

J Cell Sci. 2011 Feb 15;124(Pt 4):589-99. doi: 10.1242/jcs.072421. Epub 2011 Jan 25.

Abstract

Signal-peptide-mediated ER localization of mRNAs encoding for membrane and secreted proteins, and RNA-zipcode-mediated intracellular targeting of mRNAs encoding for cytosolic proteins are two well-known mechanisms for mRNA localization. Here, we report a previously unidentified mechanism by which mRNA encoding for Dia1, a cytosolic protein without the signal peptide, is localized to the perinuclear ER in an RNA-zipcode-independent manner in fibroblasts. Dia1 mRNA localization is also independent of the actin and microtubule cytoskeleton but requires translation and the association of Dia1 nascent peptide with the ribosome-mRNA complex. Sequence mapping suggests that interactions of the GTPase binding domain of Dia1 peptide with active Rho are important for Dia1 mRNA localization. This mechanism can override the β-actin RNA zipcode and redirect β-actin mRNA to the perinuclear region, providing a new way to manipulate intracellular mRNA localization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions
  • Actins / genetics
  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biological Transport
  • Cells, Cultured
  • Chick Embryo
  • Chickens
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Fibroblasts / metabolism
  • Formins
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Protein Binding
  • Protein Transport
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • 3' Untranslated Regions
  • Actins
  • Adaptor Proteins, Signal Transducing
  • DIAPH1 protein, human
  • Formins
  • Microfilament Proteins
  • RNA, Messenger
  • Guanosine Triphosphate
  • rhoA GTP-Binding Protein