Control of translation by eukaryotic mRNA transcript leaders-Insights from high-throughput assays and computational modeling.

Abstract

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. TL cis-regulatory elements and their corresponding trans-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.