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Montreal Bioinformatics Users Group

MonBUG (Montreal Bioinformatics Users Group) is an association of researchers, professionals and students in the greater Montreal area who have an interest in the field of bioinformatics.

Through monthly presentations we present our work, ask questions, share ideas, tips and tricks.

Meetings are held either at the Institut de Recherches Cliniques de Montréal (IRCM), the Institute for Research in Immunology and Cancer (IRIC) or at McGill university, and are free and open to all.

MonBUG is based on the highly successful VanBUG initiative and we also have a sister organization in Toronto, TorBUG.


October meeting

We have another great line-up.
To register, and for all the details, go to Meetup, http://meetup.com/monbug.

Sandrine Moreira, who did her PhD in bioinformatics at Université de Montréal, will be coming from Columbia University in New York to present her post-PhD research on non conventional microbial genomes.
Rached Alkallas will be presenting his research published just this month in Nature Communications, “Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer’s disease.”

Agenda
17:00 – 17:05 Introduction and community announcements
17:05 – 17:35 “Decryption of mitochondrial genes in diplonemids by RNA editing and trans-splicing”, Sandrine Moreira, post-PhD Landweller lab
17:35- 18:00 Break, with snacks and refreshments
18:00 – 18:30 “Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer’s disease.”, Rached Alkallas, PhD student Najafabadi and Watson lab

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Don’t forget to subscribe to our revived YouTube channel, which we will now be updating regularly.
https://www.youtube.com/channel/UCpLqBEa6o6nmoI9zLtOHCPw

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Here is the link to Rached’s article.
https://www.nature.com/articles/s41467-017-00867-z

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Here is a summary of the talk that will be given by Sandrine.

Decryption of mitochondrial genes in diplonemids by RNA editing and trans-splicing

Thanks to new high throughput sequencing technologies and automatic annotation pipelines, proceeding from an eppendorf tube to a genbank file can be achieved in a single mouse click or so, for some species. Others, however, fiercely resist bioinformaticians with their confounding genomic complexity. Ciliates and Diplonemids are one of them. My work is centered on the discovery of new strategies for encrypting genetic information in eukaryotes with unconventional genome architecture, and the identification of molecular decoding processes. I will essentially describe the work performed on diplonemids during my Ph.D. Diplonemids are a group of poorly studied marine protists. Unexpectedly, metagenomic studies have recently ranked this group as one of the most diverse and the most cosmopolitan in the oceans. Yet, their most distinctive feature is their multipartite mitochondrial genome with genes in pieces, and encryption by nucleotide deletions and substitutions. In contrast to all other organisms, their mitochondrial genes are systematically fragmented in pieces (modules) that are scattered across hundreds of small circular chromosomes. Gene pieces are transcribed independently into RNAs, that are then trans-spliced in the correct order, resembling a genomic jigsaw puzzle. Genes are further decrypted at the RNA level through RNA editing by polyuridylation at the junction of gene pieces and substitutions of A-to-I and C-to-T. Such a diverse arsenal of mitochondrial post-transcriptional processes is highly exceptional.

Using a bioinformatics approach, I have first reconstructed the mitochondrial transcriptome from RNA-seq libraries, second completed the chromosome catalogue from DNA-seq libraries, and finally annotated mitochondrial chromosomes. Genes were barely recognizable due to their extreme divergence. The gene complement contains 10 protein genes of the respiratory chain, the small and large ribosomal subunits and six new genes including one that presents alternative trans-splicing isoforms. Moreover, by comparing DNA and mature RNA sequences, we discovered that the RNA message is edited. In total, there are 216 uridines added in 14 genes with up to 29 U insertions, and 114 positions edited by deamination (A-to-I or C-to-T) among seven genes.

In order to identify the machinery that processes mitochondrial RNAs, the nuclear genome has been sequenced. I have then assembled and annotated the genome. This machinery is probably unique and complex because no cis signal or trans actor typical for known splicing machineries have been found. I have identified promising protein candidates that are worth to be tested experimentally, notably RNA ligases, numerous members of the PPR family involved in plants RNA editing and deaminases.

During my thesis, we have identified new types of post-transcriptional RNA processing in diplonemid mitochondria and identified new promising candidates for the machinery. A system capable of joining precisely or editing RNAs could find biotechnological applications. From an evolutionary perspective, the discovery of new molecular systems gives insight into the process of gene recruitment, adaptation to new functions and establishment of complex molecular machineries.

 


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