FRIDAY 18 July 2014 at 2:00pm
*** Please note this seminar will be on a FRIDAY at 2:00pm ***
Title: “Plasmodium falciparum ribosomal dosage controls a novel mechanism to regulate growth in response to temperature variation”
Speaker: Dr. Indu Sharma
Hampton University
Abstract:
Temperature is a critical determinant of malaria transmission as the parasite must survive in both vertebrate and invertebrate hosts. Plasmodium species confront dramatic temperature shifts in during its life cycle. Unlike bacteria, Plasmodium cannot slow down or retard its growth in response to adverse environmental conditions. Plasmodium species confront the dramatic temperature shifts utilizing three types of ribosomal genes: during asexual stages (A type rRNA), in gametocytes in the human host (S1rRNA) and during development in mosquito vector (S2 rRNA). Mosquito development (both aquatic and adult life) is nonlinear with little or no development below 16°C, optimal development occurs at 22-28°C and followed by a rapid non linear decline and lethal consequences above 34°C. It takes 10-12 days for P. falciparum to complete its developmental cycle in the mosquito at 22-28°C. Above 28°C temperature, the mosquito develops faster and has a shorter life span, a maximum of 6 days, which is too short for the parasite to complete its developmental cycle. And between 16-22°C, the mosquito development is delayed/longer and the parasite adjusts by extending its progression. We identified the function of a non-coding RNA which is expressed in response to temperature modulation as the parasite transitions from human host to mosquito vector. This long noncoding RNA (truRNA) is transcribed by RNA polymerase I. There are two copies of the noncoding RNA in the P. falciparum genome located upstream of the S2 rRNA gene on chromosomes 11 and 13. Comparative sequence analysis suggests the presence of truRNA in all P. falciparum strains (both established lab lines as well as clinical isolates; Plasmodium falciparum genomic database, Broad Institute, Boston, MA) with >98% sequence similarity. We monitored the expression of S2 rRNA and truRNA transcripts over a temperature range of 37°C-26°C-37°C. Our data suggest that above 30°C, S2 rRNA and truRNA are unstable with half-life of 10 and 15 minutes respectively. The single and double gene knockouts for truRNA either leads to 50% reduction in processed S2rRNA or 100% reduction respectively. These findings point in the direction that the parasite adjusts its protein synthesis machinery during its development in mosquito in response to diurnal temperature variation in nature. Four proteins were identified PF10_0068, PF08_0074, PF10_0115 and S13 ribosomal protein. Protein sequence analysis of these proteins revealed RGG/RSG motif in PF10_0068 (putative RNA binding protein) and PF08_0074 (PfALBA1 protein) which is a potential methylation site for arginine residue. Indirect evidence suggests that truRNA and these proteins possibly form a multi ribonucleoprotein complexes (MRNPs) and might play a role in the post transcriptional processing of precursor S2 rRNA transcripts to generate mature S2 ribosomes hence meeting the cell’s requirement for protein synthesis in response to temperature modulation.
Host: Dr. Rose Jagus Ph.D.