Control of translation by eukaryoticmRNAtranscript leaders-Insights from high-throughput assays and computational modeling

Eukaryotic gene expression is tightly regulated during translation of mRNA to protein. Mis-regulation of translation can lead to aberrant proteins which accumulate in cancers and cause neurodegenerative diseases. Foundational studies on model genes established fundamental roles for mRNA 5 ' transcript leader (TL) sequences in controlling ribosome recruitment, scanning, and initiation. TLcis-regulatory elements and their correspondingtrans-acting factors control cap-dependent initiation under unstressed conditions. Under stress, cap-dependent initiation is suppressed, and specific mRNA structures and sequences promote translation of stress-responsive transcripts to remodel the proteome. In this review, we summarize current knowledge of TL functions in translation initiation. We focus on insights from high-throughput analyses of ribosome occupancy, mRNA structure, RNA Binding Protein occupancy, and massively parallel reporter assays. These data-driven approaches, coupled with computational analyses and modeling, have paved the way for a comprehensive understanding of TL functions. Finally, we will discuss areas of future research on the roles of mRNA sequences and structures in translation. This article is categorized under: Translation > Translation Mechanisms RNA Evolution and Genomics > Computational Analyses of RNA RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems