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Publications of the Week

Loss of m1acp3Ψ Ribosomal RNA Modification Is a Major Feature of Cancer

By May 19, 2020May 25th, 2020No Comments

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This week we profile a recent publication in Cell Reports from Dr. Artem Babaian (pictured)
in the laboratory of Dr. Dixie Mager at the Terry Fox Laboratory at BC Cancer.

What is the significance of the findings in this publication?

My passion project of the last three years was recently published in Cell Reports. I made this discovery back in March of 2017 during my PhD. As soon as I saw Figure 1A, I stopped all my PhD work and switched to this project full time. I scrapped together the resources/grants/collaborators to make this happen because I believed in it. In that time I also managed to squeeze in PhD thesis (barely).

I found that there is a ribosomal RNA hyper-modification called 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (macpΨ) that is perturbed in human cancers. The modification is 1.5 billion years conserved (all eukaryotes have it, no exceptions). 45% of colorectal cancer (CRC) tumours have a partial loss of this modification, and the same phenotype is seen in >22 distinct types of cancers. I like to make the comparison that only 36% of CRCs have point mutations to KRAS.

What are the next steps for this research?

This really is the starting point for this research. I’m now diving into the molecular mechanisms underlying this phenomenon. What is the cause of modification loss? How is it impacting translation in cancer cells? Is this an ‘epigenetic driver mutation’? And finally, can we find a small molecule that selectively inhibits these cancer ribosomes missing the modification.

This work was funded by:

This research was supported by The Roman M. Babicki Fellowship for Medical Research, a Leukemia and Lymphoma Society of Canada innovation grant, and an AWS Research Credit grant.

To learn more about Dr. Babaian’s work, check out his Spotlight interview, where he discusses his research into endogenous retroviruses and cancer.

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