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  4. Impaired Striatal Akt Signaling Disrupts Dopamine Homeostasis and Increases Feeding

Impaired Striatal Akt Signaling Disrupts Dopamine Homeostasis and Increases Feeding

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Author(s)
Bonocora, Richard P.
•
Abel, Ethan V.
•
Shub, David A.
•
Zeng, Qinglu
Date Issued
September 2011
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences (PNAS)
Citation
Bonocora, R. P. et al. “A Homing Endonuclease and the 50-nt Ribosomal Bypass Sequence of Phage T4 Constitute a Mobile DNA Cassette.” Proceedings of the National Academy of Sciences 108.39 (2011): 16351–16356. Web. 13 Apr. 2012.
Version
Final published version
Abstract
Since its initial description more than two decades ago, the ribosome bypass (or “hop”) sequence of phage T4 stands out as a uniquely extreme example of programmed translational frameshifting. The gene for a DNA topoisomerase subunit of T4 has been split by a 1-kb insertion into two genes that retain topoisomerase function. A second 50-nt insertion, beginning with an in-phase stop codon, is inserted near the start of the newly created downstream gene 60. Instead of terminating at this stop codon, approximately half of the ribosomes skip 50 nucleotides and continue translation in a new reading frame. However, no functions, regulatory or otherwise, have been imputed for the truncated peptide that results from termination at codon 46 or for the bypass sequence itself. Moreover, how this unusual mRNA organization arose and why it is maintained have never been explained. We show here that a homing endonuclease (MobA) is encoded in the insertion that created gene 60, and the mobA gene together with the bypass sequence constitute a mobile DNA cassette. The bypass sequence provides protection against self-cleavage by the nuclease, whereas the nuclease promotes horizontal spread of the entire cassette to related bacteriophages. Group I introns frequently provide protection against self-cleavage by associated homing endonucleases. We present a scenario by which the bypass sequence, which is otherwise a unique genetic element, might have been derived from a degenerate group I intron.
Description
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1107633108/-/DCSupplemental.
MIT Department
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
http://hdl.handle.net/1721.1/70026
DOI of Published Version
http://dx.doi.org/10.1073/pnas.1107633108
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