Noncanonical Regulation of mRNA Translation
Regulation of mRNA translation is crucial to cellular homeostasis, development, and growth. The failure to tightly regulate mRNA translation causes several diseases including developmental disorders and cancer. Canonical regulation of mRNA translation ensures the fidelity of mRNA initiation, elongation, and termination. However, these canonical pathways cannot explain several aspects of mRNA translation in cells, for example: 1) how mRNA modifications contribute to its fate and function; 2) how organelle-coupled mRNA translation at the endoplasmic reticulum (ER) and mitochondria are regulated; 3) how the information in the 5’- and 3’-untranslated regions (UTRs) affects mRNAs translation outcome. Also, how these pathways contribute to cellular homeostasis or dysregulation in human diseases in not fully understood. This highlights the importance of studying noncanonical mRNA translation pathways.
We apply a diverse set of contemporary molecular, cellular, and in vivo approaches, including RNA and protein biochemistry, RNA-sequencing, ribosome profiling, CRISPR- and chemical-screening, and microscopy to provide mechanistic insights into these pathways. We utilize stem cell differentiation, cancer cells, and genetic mouse models to unravel the physiological significance of noncanonical mRNA translation pathways in the context of development and disease.