Mechanism and regulation of mRNA polyadenylation

  1. Diana F. Colgan and
  2. James L. Manley1
  1. Department of Biological Sciences, Columbia University, New York, New York 10027 USA

This extract was created in the absence of an abstract.

A poly(A) tail is found at the 3′ end of nearly every fully processed eukaryotic mRNA and has been suggested to influence virtually all aspects of mRNA metabolism. Its proposed functions include conferring mRNA stability, promoting an mRNA’s translational efficiency, and having a role in transport of processed mRNA from the nucleus to the cytoplasm (for recent reviews, see Lewis et al. 1995; Sachs et al. 1997; Wickens et al. 1997). The reaction that catalyzes the addition of the poly(A) tail, an endonucleolytic cleavage followed by poly(A) synthesis, has also been the focus of intense investigation but, until recently, may have been viewed as a process that follows a predictable, isolated, and invariant path. Yet, as more is learned about 3′-end formation, it becomes clear that the function of the polyadenylation machinery extends beyond simply adding poly(A) tails to mRNAs.

The first report of a component of the mammalian cleavage and polyadenylation machinery was nearly 40 years ago in a paper describing an activity found in thymus nuclei extracts that could synthesize poly(A) from ATP (Edmonds and Abrams 1960). Ten years passed before poly(A) tails were identified as a post-transcriptionally added modification of mRNA 3′ termini and a possible function was assigned to poly(A) polymerase (Darnell et al. 1971; Edmonds et al. 1971; Lee et al. 1971). But nearly another decade elapsed before it was found that transcription proceeds past the polyadenylation site, revealing that a mechanism other than transcriptional termination generates mRNA 3′ ends (Ford and Hsu 1978; Nevins and Darnell 1978;Manley et al. 1982). The pace of discovery quickened with the development of cell extracts that reproduce the reaction, and this allowed the subsequent and still ongoing biochemical characterization of mRNA 3′-end formation (Manley 1983; Moore and Sharp 1984, …

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