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Elucidating the role of alternative trans-splicing in the mRNA abundance regulation of Leishmania.

Leishmania is a genus of protozoan parasites that cause the disease leishmaniasis in humans and a wide array of vertebrate animals. The parasite exhibits a remarkable gene expression system where genes lack individual RNA polymerase II promoters and are therefore not individually controllable by transcription factors. Instead, genes are transcribed constitutively in long polycistronic units of functionally unrelated genes and co-transcriptionally processed to individual mRNAs per gene during a process called 'trans-splicing'. During trans-splicing, mRNAs receive a fixed 39 nucleotide sequence at their 5' end called 'spliced-leader'. The location where this spliced-leader is added is variable, resulting in different possible transcript lengths for a single gene (alternative trans-splicing). The abundance of mRNA per gene appears to be regulated entirely post-transcriptionally, however, it is currently unclear how this occurs. This project aims to determine the role of alternative trans-splicing in the mRNA abundance regulation of Leishmania. As this process determines the length of the transcript, we hypothesise that it affect the abundance of a transcript by altering its stability and/or included regulatory motifs. For the first time, we will make use of long read mRNA sequencing (PacBio) to study the changes in transcript repertoires during different life stages of Leishmania donovani. Additionally, we aim to identify the motifs and/or RNA structural patterns which regulate the location and usage frequency of alternative trans-splicing and polyadenylation sites. This will be investigated making use of state-of-the art pattern finding and classification approaches.
Date:1 Apr 2019  →  30 Mar 2020
Disciplines:Analysis of next-generation sequence data, Infectious diseases, Parasitology, Transcription and translation