Nucleic Acids Research Advance Access originally published online on February 3, 2008
Nucleic Acids Research 2008 36(5):1634-1644; doi:10.1093/nar/gkn019
Nucleic Acids Research, 2008, Vol. 36, No. 5 1634-1644
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Deadenylation-independent stage-specific mRNA degradation in Leishmania
Research Centre in Infectious Diseases, CHUL Research Centre and Department of Medical Biology, Faculty of Medicine, Laval University, Quebec, Canada
*To whom correspondence should be addressed. Tel: +1 418 654 2705; Fax: +1 418 654 2715; Email: barbara.papadopoulou{at}crchul.ulaval.ca
Received December 4, 2007. Revised January 10, 2008. Accepted January 10, 2008.
The life cycle of Leishmania alternates between developmental forms residing within the insect vector (e.g. promastigotes) and the mammalian host (amastigotes). In Leishmania nearly all control of gene expression is post-transcriptional and involves sequences in the 3'-untranslated regions (3'UTRs) of mRNAs. Very little is known as to how these cis-elements regulate RNA turnover and translation rates in trypanosomatids and nothing is known about mRNA degradation mechanisms in Leishmania in particular. Here, we use the amastin mRNA—an amastigote-specific transcript—as a model and show that a
100 nt U-rich element (URE) within its 3'UTR significantly accounts for developmental regulation. RNase-H-RNA blot analysis revealed that a major part of the rapid promastigote-specific degradation of the amastin mRNA is not initiated by deadenylation. This is in contrast to the amastin mRNA in amastigotes and to reporter RNAs lacking the URE, which, in common with most eukaryotic mRNAs studied to-date, are deadenylated before being degraded. Moreover, our analysis did not reveal a role for decapping in the stage-specific degradation of the amastin mRNA. Overall, these results suggest that degradation of the amastin mRNA of Leishmania is likely to be bi-phasic, the first phase being stage-specific and dependent on an unusual URE-mediated pathway of mRNA degradation.
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