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Molecular and Cellular Biology, June 2008, p. 3873-3881, Vol. 28, No. 11
0270-7306/08/$08.00+0     doi:10.1128/MCB.02153-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Autoregulation of Npl3, a Yeast SR Protein, Requires a Novel Downstream Region and Serine Phosphorylation{triangledown}

Mette K. Lund,1 Tracy L. Kress,2 and Christine Guthrie2*

Department of Molecular Biology, University of Aarhus, C. F. Mollers Alle, 8000 Aarhus C, Denmark,1 Department of Biochemistry and Biophysics, UCSF Medical School, Genentech Hall, 600 16th Street, San Francisco, California 941432

Received 3 December 2007/ Returned for modification 25 February 2008/ Accepted 26 March 2008

Npl3 is an SR-like protein with documented roles in mRNA export and transcription termination. Maintaining appropriate levels of Npl3 protein is critical for cell survival. Here we show that Npl3 negatively regulates its own expression via modulation of its mRNA levels. By creating gene chimeras, we demonstrate that the region downstream of the coding sequence of Npl3 is necessary and sufficient to confer regulation. The use of different polyadenylation sites in this region results in at least two stable RNAs; read-through of these sites causes the formation of 3'-extended RNAs that are highly unstable and therefore largely unproductive. Increasing the amount of Npl3 protein promotes read-through. Notably, the loss of Npl3 phosphorylation promotes the use of the productive polyadenylation sites, resulting in elevated levels of Npl3 protein. We propose that proper levels of Npl3 protein are achieved by a negative feedback loop in which phosphorylated Npl3 suppresses efficient recognition of the productive processing signals in its own transcript.


* Corresponding author. Mailing address: Department of Biochemistry and Biophysics, Genentech Hall, 600 16th Street, San Francisco, CA 94143-2200. Phone: (415) 476-2321. Fax: (415) 502-5306. E-mail: guthrie{at}biochem.ucsf.edu

{triangledown} Published ahead of print on 7 April 2008.


Molecular and Cellular Biology, June 2008, p. 3873-3881, Vol. 28, No. 11
0270-7306/08/$08.00+0     doi:10.1128/MCB.02153-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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