Utilising capture-seq to identify noncoding RNAs in the ribosomal RNA gene repeat intergenic spacer as potential drivers of malignancy — ASN Events

Utilising capture-seq to identify noncoding RNAs in the ribosomal RNA gene repeat intergenic spacer as potential drivers of malignancy (#260)

Jessica Fitch 1 2 , Kate Hannan 3 , Ross Hannan 3 , Sebastian Schmeier 2 , Austen Ganley 1
  1. University of Auckland, Auckland, North Island, New Zealand
  2. Massey University, Auckland, North Island, New Zealand
  3. Australian National University , Canberra, New South Wales, Australia

Cancer is one of the leading causes of mortality in developed countries. A hallmark characteristic of cancer cells is phenotypic variation of the nucleolus, the site of ribosomal RNA gene (rDNA) transcription and ribosome pre-biogenesis. The rDNA encodes ribosomal RNA, which is the major structural and catalytic component of ribosomes. Accordingly, rDNA transcription is a key regulator of cell proliferation and is strongly implicated in cancer. Interestingly, in addition to rRNA transcription, a number of non-coding RNAs (ncRNAS) are transcribed from the rDNA, although almost none of these have been characterised. Given that some ncRNAs from other regions of the genome have been implicated in cancer, and that preliminary evidence suggests rDNA ncRNA transcription is increased in cancer, we wanted to explore whether any rDNA ncRNAs are involved in cancer. The goal of my project is to identify the full complement of rDNA ncRNAs in the Eu-Myc mouse lymphoma model. To achieve this, I am using the hybridisation-based capture technique, combined with RNA-seq. Using bioinformatic tools, I will assess which transcripts change their expression when ribosome biogenesis is impacted. Differentially expressed ncRNAs will be selected for further validation using conventional PCR methods, and retroviral knockdown/overexpression approaches will be used to investigate the roles of these ncRNAs, particularly in malignancy. This project will create a comprehensive catalog of ncRNAs in the rDNA, and will assess the potential of these rDNA ncRNAs as novel targets for therapy, and as diagnostic and prognostic markers of cancer.

#LorneGenome