LIVER-REGENERATION .5. POSTTRANSCRIPTIONAL REGULATION OF GENE-EXPRESSION IN LIVER-REGENERATION - ROLE OF MESSENGER-RNA STABILITY

The rentry of hepatocytes and nonparenchymal cells from the normal qui escent G(0) phase into the cell cycle during liver regeneration after 70% partial hepatectomy results in the discrete modulation of mRNA tra nscripts for many different genes, The modulation of steady-state leve ls of transcripts for genes involved in hepatocyte growth and replicat ion during liver regeneration indicates that gene expression is regula ted not only transcriptionally but also posttranscriptionally. In fact , posttranscriptional control appears to be the primary mechanism of r egulating gene expression after the first 3 h after partial hepatectom y, Alteration in transcript stability is a key posttranscriptional reg ulatory mechanism used by the regenerating liver to modulate the stead y-state transcript levels of multiple genes, Even genes that are trans criptionally activated during liver regeneration exhibit posttranscrip tional control at the level of transcript stability, Moreover, the abu ndance of mRNA binding proteins, as well as translational activity and rate of poly(A) tail removal, are modulated and appear to influence t ranscript stability during liver regeneration, However, alteration of transcript stability is not the sole posttranscriptional mechanism reg ulating steady-state levels, Posttranscriptional control also occurs a t the level of alternative splicing, stabilization of heterogeneous nu clear (hn) RNA, and hnRNA processing, Moreover, the role of nucleocyto plasmic transport of mature mRNA during liver regeneration is still un defined, Thus, during liver regeneration gene expression is regulated at multiple levels after the initial synthesis of hnRNA, By understand ing the role of posttranscriptional mechanisms in regulating steady-st ate transcript levels in an in vivo model of normal growth, we will be gin to appreciate its role in the genesis of abnormal growth.