TISSUE-SPECIFIC EXPRESSION OF HUMAN LIPOPROTEIN-LIPASE - EFFECT OF THE 3'-UNTRANSLATED REGION ON TRANSLATION

Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle, In these tissues, the regulation of LPL is complex and often opposite in respo nse to the same physiologic stimulus, In addition, much regulation of LPL occurs post-transcriptionally. The hu man LPL cDNA is characterize d by a long 3'-untranslated region, which has two polyadenylation sign als, In this report, human adipose tissue expressed two LPL mRNA speci es (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed pr edominantly the longer 3.6-kb mRNA form. To determine whether there wa s any functional significance to this tissue-specific mRNA expression, poly(A)-enriched RNA from adipose tissue and muscle were translated i n vitro, and the poly(A)-enriched RNA from muscle was more efficiently translated into LPL protein, The increased translatability of the 3.6 -kb form was also demonstrated by cloning the full-length 3.2- and 3.6 -kb LPL cDNA forms, followed by in vitro translation of in vitro prepa red transcripts, To confirm that this increased efficiency of translat ion occurred in vivo, Chinese hamster ovary cells were transfected wit h the 3.2- and 3.6-kb LPL cDNAs, Cells transfected with the 3.6-kb con struct demonstrated increased LPL activity and synthesis, despite no i ncrease in levels of LPL mRNA. Thus, human muscle expresses the 3.6-kb form of LPL due to a non-random choice of polyadenylation signals, an d this form is more efficiently translated than the 3.2-kb form.