The balance sheet for transcription: an analysis of nuclear RNA metabolismin mammalian cells

The control of RNA synthesis from protein-coding genes is fundamental in de termining the various cell types of higher eukaryotes. The activation of th ese genes is driven by promoter complexes, and RNA synthesis is performed b y an enzyme mega-complex--the RNA polymerase II holoenzyme. These two compl exes are the fundamental components required to initiate gene expression an d generate the primary transcripts that, after processing, yield mRNAs that pass to the cytoplasm where protein synthesis occurs. But although this ge ne expression pathway has been studied intensively, aspects of RNA metaboli sm remain difficult to comprehend. In particular, it is unclear why >95% of RNA polymerized by polymerase II remains in the nucleus, where it is recyc led. To explain this apparent paradox, this review presents a detailed desc ription of nuclear RNA (nRNA) metabolism in mammalian cells. We evaluate th e number of active transcription units, discuss the distribution of polymer ases on active genes, and assess the efficiency with which the products mat ure and pass to the cytoplasm. Differences between the behavior of mRNAs on this productive pathway and primary transcripts that never leave the nucle us lead us to propose that these represent distinct populations. We discuss possible roles for nonproductive RNAs and present a model to describe the metabolism of these RNAs in the nuclei of mammalian cells.