Post-transcriptional Repair of a Split Heat Shock Protein 90 Gene by mRNA trans-Splicing

Nageshan, Rishi Kumar and Roy, Nainita and Hehl, Adrian B and Tatu, Utpal (2011) Post-transcriptional Repair of a Split Heat Shock Protein 90 Gene by mRNA trans-Splicing. In: Journal of Biological Chemistry, 286 (9). pp. 7116-7122.

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Abstract

Heat shock protein 90 participates in diverse biological processes ranging from protein folding, cell cycle, signal transduction and development to evolution in all eukaryotes. It is also critically involved in regulating growth of protozoa such as Dictyostelium discoideum, Leishmania donovani, Plasmodium falciparum, Trypanosoma cruzi, and Trypanosoma evansi. Selective inhibition of Hsp90 has also been explored as an intervention strategy against important human diseases such as cancer, malaria, or trypanosomiasis. Giardia lamblia, a simple protozoan parasite of humans and animals, is an important cause of diarrheal disease with significant morbidity and some mortality in tropical countries. Here we show that the G. lamblia cytosolic hsp90 ( glhsp90) is split in two similar sized fragments located 777 kb apart on the same scaffold. Intrigued by this unique arrangement, which appears to be specific for the Giardiinae, we have investigated the biosynthesis of GlHsp90. We used genome sequencing to confirm the split nature of the giardial hsp90. However, a specific antibody raised against the peptide detected a product with a mass of about 80 kDa, suggesting a post-transcriptional rescue of the genomic defect. We show evidence for the joining of the two independent Hsp90 transcripts in-trans to one long mature mRNA presumably by RNA splicing. The splicing junction carries hallmarks of classical cis-spliced introns, suggesting that the regular cis-splicing machinery may be sufficient for repair of the open reading frame. A complementary 26-nt sequence in the ``intron'' regions adjacent to the splice sites may assist in positioning the two pre-mRNAs for processing. This is the first example of post-transcriptional rescue of a split gene by trans-splicing.

Item Type:	Journal Article
Publication:	Journal of Biological Chemistry
Publisher:	The American Society for Biochemistry and Molecular Biology
Additional Information:	Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	24 Mar 2011 06:23
Last Modified:	24 Mar 2011 06:23
URI:	http://eprints.iisc.ac.in/id/eprint/36194

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