RT Journal Article
SR Electronic
T1 Regulatory start-stop elements in 5’ untranslated regions pervasively modulate translation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.26.453809
DO 10.1101/2021.07.26.453809
A1 Justin Rendleman
A1 Mahabub Pasha Mohammad
A1 Matthew Pressler
A1 Shuvadeep Maity
A1 Vladislava Hronová
A1 Zhaofeng Gao
A1 Anna Herrmannová
A1 Amy Lei
A1 Kristina Allgoewer
A1 Daniel Sultanov
A1 Will Edward Hinckley
A1 Krzysztof J. Szkop
A1 Ivan Topisirovic
A1 Ola Larsson
A1 Maria Hatzoglou
A1 Leoš Shivaya Valášek
A1 Christine Vogel
YR 2021
UL http://biorxiv.org/content/early/2021/07/26/2021.07.26.453809.abstract
AB Translation includes initiation, elongation, and termination, followed by ribosome recycling. We characterize a new sequence element in 5’ untranslated regions that consists of an adjacent start and stop codon and thereby excludes elongation. In these start-stop elements, an initiating ribosome is simultaneously positioned for termination without having translocated. At the example of activating transcription factor 4 (ATF4), we demonstrate that start-stops modify downstream re-initiation, thereby repressing translation of upstream open reading frames and enhancing ATF4’s inducibility under stress. Start-stop elements are abundant in both mammals and yeast and affect key regulators such as DROSHA and the oncogenic transcription factor NFIA. They provide a unique regulatory layer that impedes ribosome scanning without the energy-expensive peptide production that accompanies upstream open reading frames.One-Sentence Summary Regulatory start-stop elements in the 5’UTR are hitherto unappreciated contributors to 5’ UTR code and alter the translatome.Competing Interest StatementThe authors have declared no competing interest.