Peer-Reviewed Publication on Cancer Cells

Protein synthesis is a process central to all life on Earth, including mammalian cells. During this process, ribosomes attach to mRNA strands and translate them into proteins using amino acids. Under stress, ribosomes can stall. Ribosome profiling, a technique that creates a snapshot of active ribosomes in a cell by sequencing ribosome-protected mRNA fragments, captures a snapshot of ribosomes along transcripts and can detect such stalling events. For his project, Mark used a computational approach to research ribosome stalling trends in ribosome profiling and mRNA sequencing data from amino acid-starved pancreatic cancer cells, aiming to explore whether the pattern of ribosome distribution along transcripts under normal conditions can predict the degree of ribosome stalling under stress. He hypothesized that ribosomes would stall more along “elongation-limited” transcripts that have fewer ribosome footprints near the start and stop codons than “initiation-limited” transcripts that have a large fraction of footprints at the start codon. Indeed, Mark found his hypothesis to be true, but observed no relationship between read (a DNA sequence from one fragment a fragment of DNA) density near start and stop codons and disparities between mRNA sequencing reads and ribosome profiling reads. This research identifies an important relationship between read distribution and propensity for ribosomes to stall.