Assembling an intermediate filament network by dynamic cotranslation

Lynne Chang1, Yaron Shav-Tal, Tatjana Trcek

  • 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. l-chang1@northwestern.edu

Insights

Researchers observed messenger RNA (mRNA) and protein interactions in vivo. Messenger ribonucleoproteins (mRNPs) move along microtubules, initiating translation upon stopping, forming "translation factories" for protein synthesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cytoskeletal Dynamics

Background:

  • Intermediate filaments (IFs) form essential cytoskeletal networks.
  • Peripherin is a key component of neuronal intermediate filaments.
  • Understanding the regulation of peripherin synthesis and assembly is crucial for neuronal function.

Purpose of the Study:

  • To investigate the in vivo dynamics of peripherin messenger RNA (mRNA) and its protein product.
  • To elucidate the mechanisms governing mRNA transport, translation, and protein assembly.
  • To define the relationship between mRNA dynamics and cytoskeletal organization.

Main Methods:

  • Studied the synthesis and assembly of peripherin intermediate filaments (IFs) in vivo.
  • Tracked the movement and localization of peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]).
  • Analyzed the translational status and assembly of peripherin protein.

Main Results:

  • Peripherin mRNPs predominantly move along microtubules (MT).
  • mRNPs are translationally silent during movement, initiating translation upon cessation of motion.
  • Multiple mRNAs can cluster in mRNPs, forming "translation factories" for amplified protein synthesis.
  • Peripherin undergoes cotranslational assembly into precursor particles for IFs.
  • mRNA clustering depends on MT, RNA regulatory sequences, and the nascent protein.

Conclusions:

  • Dynamic cotranslation links the motility and targeting of peripherin mRNPs, translational control, and IF cytoskeletal assembly.
  • This process allows for localized and amplified protein synthesis, contributing to cytoskeletal organization.
  • The findings provide new insights into the regulation of protein synthesis and cytoskeletal dynamics in vivo.

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