4.7 Article

Assembling an intermediate filament network by dynamic cotranslation

Journal

JOURNAL OF CELL BIOLOGY
Volume 172, Issue 5, Pages 747-758

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200511033

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Funding

  1. NIAMS NIH HHS [R01 AR041480, AR41480] Funding Source: Medline
  2. NIBIB NIH HHS [R01 EB002060, EB2060] Funding Source: Medline
  3. NIGMS NIH HHS [R37 GM036806, R01 GM036806, GM-36806-16] Funding Source: Medline

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We have been able to observe the dynamic interactions between a specific messenger RNA (mRNA) and its protein product in vivo by studying the synthesis and assembly of peripherin intermediate filaments (IFs). The results show that peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]) move mainly along microtubules (MT). These mRNPs are translationally silent, initiating translation when they cease moving. Many peripherin mRNPs contain multiple mRNAs, possibly amplifying the total amount of protein synthesized within these translation factories. This mRNA clustering is dependent on MT, regulatory sequences within the RNA and the nascent protein. Peripherin is cotranslationally assembled into insoluble, nonfilamentous particles that are precursors to the long IF that form extensive cytoskeletal networks. The results show that the motility and targeting of peripherin mRNPs, their translational control, and the assembly of an IF cytoskeletal system are linked together in a process we have termed dynamic cotranslation.

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