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Published 27 February 2006. doi:10.1083/jcb.200511033
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 5, 747-758
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Article

 Assembling an intermediate filament network by dynamic cotranslation

Lynne Chang1, Yaron Shav-Tal2,3, Tatjana Trcek3, Robert H. Singer3, and Robert D. Goldman1

1 Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611
2 Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
3 Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461

Correspondence to Lynne Chang: l-chang1{at}northwestern.edu

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.

Abbreviations used in this paper: 3D, three-dimensional; CDS, coding sequence; DM, differentiation medium; ECFP, enhanced CFP; IF, intermediate filament; mRNP, messenger RNP; MT, microtubules; TFI, total fluorescent intensity; ULF, unit-length filament; UTR, untranslated region.


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