Translation regulation

Translation regulation in Apicomplexans

The malarial parasite, Plasmodium falciparum, is known to have one of the most AT-rich genomes with the AT-content as high as ~80%. High AT content in the parasite's genome leads to increased chances of finding upstream AUG and upstream Open Reading Frames (uORFs), with an average of 3 to 4 uORFs per coding sequence(Srinivas et al., 2016). Upstream open reading frames (uORFs) are known to repress the translation of downstream ORFs in Plasmodium falciparum (Kumar et al., 2015) as in other eukaryotes. Despite the presence of numerous uORFs, the ribosomes are still able to reach the translation initiation site (TIS) of the CDS and translate it either by leaky scanning or by reinitiation. We have reported detailed in-silico as well as in-vivo analysis of translation initiation sites from Plasmodium falciparum. Further, we are trying to demystify the path chosen by the parasite's ribosome to translate the CDS in presence of upstream ORFs. The effect of various parameters, such as uORF length, inter-cistronic length, and Kozak sequence, on translation of a reporter gene under Pfhsp86 promoter and 5' leader with different uORFs, is being evaluated. In order to predict a genome-wide scenario with respect to translation of the CDS via leaky-scanning and/or reinitiation, we are modelling the ribosome scanning in presence of uORFs. 

More recently, we have started working on uORFs in Toxoplasma gondii and are studying their role in differentiation of the parasites from the rapidly dividing tachyzoites to the latent stages termed as bradyzoites. 

Funded by: Board for Research in Nuclear Sciences, Department of Atomic Energy, Government of India (2007/37/64/BRNS) and International Center for Genetic Engineering & Biotechnology (Grant No. CRP/22/005).

Translation initiation team