Assembling an intermediate filament network by dynamic cotranslation.
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.
Chang
Lynne
L
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. l-chang1@northwestern.edu
Shav-Tal
Yaron
Y
Trcek
Tatjana
T
Singer
Robert H
RH
Goldman
Robert D
RD
D000818:Animals; D036681:Fluorescence Recovery After Photobleaching; D006367:HeLa Cells; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007382:Intermediate Filaments / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D064531:Peripherins; D046188:Protein Modification, Translational / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012261:Ribonucleoproteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein