This webinar outlines a study that combined genome-wide and classical molecular approaches to demonstrate that translation strongly affects mRNA stability in a codon-dependent manner, ultimately influencing mRNA and protein levels in higher organisms.
Ribosomes are the most abundant RNA-binding structures in the cell, and while their main function is to decode nucleotides into amino acid sequences, translation can also affect mRNA stability depending on codon composition. This regulatory pathway is different from codon usage or bias and is known as “codon optimality” defined as the property of given codons to regulate mRNA stability in a translation-dependent manner.
In this webinar, Ariel Bazzini of the Stowers Institute for Medical Research details a study that took three independent approaches in different human cells. The team measured the decay of existing mRNAs by performing time-course RNA-seq; measured mRNA stability independent of untranslated regions (UTRs) using a vector-based library termed ORFome; and measured mRNA stability without blocking mRNA transcription using a method called SLAM-seq.
Dr. Bazzini discusses the study’s findings, which provide valuable insights into a novel and powerful regulatory pathway that may be an underlying cause of misregulated gene expression in human conditions and diseases.
Dr. Bazzini is currently an Assistant Investigator at the Stowers Institute for Medical Research where his research focuses on understanding post-transcriptional gene regulation — specifically, how mRNA translation affects mRNA stability in vertebrates. To dissect the molecular mechanisms and implications of this strong regulatory pathway, the lab uses the technical and biological advantages of the zebrafish embryo system, as well as human cell lines.
Dr. Bazzini has broad interests in RNA biology, gene regulation and development. As a graduate student in Dr. Asurmendi’s lab (INTA and University of Buenos Aires, Argentina), he studied how viruses affect host gene expression using the microRNA pathway. Following his passion for microRNAs, Dr. Bazzini joined Dr. Antonio Giraldez’s lab at Yale University. As a postdoctoral fellow, he successfully adapted a ribosome profiling technique for use in zebrafish embryos to measure translation in vivo and to ultimately show that translation affects mRNA stability based on the codon composition in zebrafish embryos, a mechanism referred to as “codon optimality.”