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Research Article

Polysome trafficking of transcripts and microRNAs in regenerating liver after partial hepatectomy

¹University of Minnesota

Submitted 4 November 2008 ; revision received 18 September 2009 ; accepted in final form 21 September 2009

ABSTRACT

Liver regeneration following 70% partial hepatectomy (PH) in rats induces > 95% of hepatocytes to undergo two rounds of semi-synchronous cell replication. Gene expression is controlled primarily by posttranscriptional processing, including changes in mRNA stability. However, the translational activity of a specific mRNA can also be modulated post-PH resulting in significant uncoupling of protein and transcript levels relative to quiescent liver for many genes including c-myc and p53. Although the precise mechanism by which this uncoupling occurs is unknown, the polysomal association of mRNA and microRNA (miRNA) can significantly modulate rate of decay as well as translational activity. Thus, we characterized the association of c-myc and p53 mRNAs, and miRNAs in the free, cytoskeletal- and membrane-bound polysome populations 3, 6 and 24 hrs after PH. The transcripts for c-myc and p53 were differentially distributed in the three discrete polysome populations and this was dramatically modulated during liver regeneration. Nascent polysome-associated p53 and c-myc proteins were also differentially expressed in the free, cytoskeletal- and membrane-bound polysomes, and significantly uncoupled from transcript levels relative to non-resected liver. At least 85 miRNAs were associated with the three polysome populations and their abundance and distribution changed significantly during liver regeneration. These data suggest that posttranscriptional control of c-myc and p53 protein expression is associated with the translocation of transcripts between the different polyribosomes. The alteration of expression for the same transcript in different polysome populations may, in part, be due to the action of miRNAs.

liver regeneration; microRNAs; polysome trafficking; c-myc