Translational regulation of Anopheles gambiae mRNAs in the midgut during Plasmodium falciparum infection

Mead, Edward A.; Li, Meng; Tu, Zhijian Jake; Zhu, Jinsong

Translational regulation of Anopheles gambiae mRNAs in the midgut during Plasmodium falciparum infection

dc.contributor.author	Mead, Edward A.	en
dc.contributor.author	Li, Meng	en
dc.contributor.author	Tu, Zhijian Jake	en
dc.contributor.author	Zhu, Jinsong	en
dc.contributor.department	Biochemistry	en
dc.date.accessioned	2012-09-14T19:06:27Z	en
dc.date.available	2012-09-14T19:06:27Z	en
dc.date.issued	2012-08-02	en
dc.date.updated	2012-09-14T19:06:27Z	en
dc.description.abstract	Background Malaria is caused by Plasmodium parasites, which are transmitted via the bites of infected Anopheline mosquitoes. Midgut invasion is a major bottleneck for Plasmodium development inside the mosquito vectors. Malaria parasites in the midgut are surrounded by a hostile environment rich in digestive enzymes, while a rapidly responding immune system recognizes Plasmodium ookinetes and recruits killing factors from the midgut and surrounding tissues, dramatically reducing the population of invading ookinetes before they can successfully traverse the midgut epithelium. Understanding molecular details of the parasite-vector interactions requires precise measurement of nascent protein synthesis in the mosquito during Plasmodium infection. Current expression profiling primarily monitors alterations in steady-state levels of mRNA, but does not address the equally critical issue of whether the proteins encoded by the mRNAs are actually synthesized. Results In this study, we used sucrose density gradient centrifugation to isolate actively translating Anopheles gambiae mRNAs based upon their association with polyribosomes (polysomes). The proportion of individual gene transcripts associated with polysomes, which is determined by RNA deep sequencing, reflects mRNA translational status. This approach led to identification of 1017 mosquito transcripts that were primarily regulated at the translational level after ingestion of Plasmodium falciparum-infected blood. Caspar, a negative regulator of the NF-kappaB transcription factor Rel2, appears to be substantially activated at the translational levels during Plasmodium infection. In addition, transcripts of Dcr1, Dcr2 and Drosha, which are involved in small RNA biosynthesis, exhibited enhanced associations with polysomes after P. falciparum challenge. This observation suggests that mosquito microRNAs may play an important role in reactions against Plasmodium invasion. Conclusions We analyzed both total cellular mRNAs and mRNAs that are associated with polysomes to simultaneously monitor transcriptomes and nascent protein synthesis in the mosquito. This approach provides more accurate information regarding the rate of protein synthesis, and identifies some mosquito factors that might have gone unrecognized because expression of these proteins is regulated mainly at the translational level rather than at the transcriptional level after mosquitoes ingest a Plasmodium-infected blood meal.	en
dc.description.version	Published version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	BMC Genomics. 2012 Aug 02;13(1):366	en
dc.identifier.doi	https://doi.org/10.1186/1471-2164-13-366	en
dc.identifier.uri	http://hdl.handle.net/10919/19002	en
dc.language.iso	en	en
dc.rights	Creative Commons Attribution 4.0 International	en
dc.rights.holder	Edward A Mead et al.; licensee BioMed Central Ltd.	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.title	Translational regulation of Anopheles gambiae mRNAs in the midgut during Plasmodium falciparum infection	en
dc.title.serial	BMC Genomics	en
dc.type	Article - Refereed	en
dc.type.dcmitype	Text	en