Translation Complex Profile Sequencing Allows Discrimination of Leaky Scanning and Reinitiation in Upstream Open Reading Frame-controlled Translation.

Authors

Dmitri E Andreev, Jack A S Tierney, Pavel V Baranov

Published in

Journal of molecular biology. Volume 436. Issue 23. Pages 168850. Dec 01, 2024. Epub Oct 30, 2024.

Abstract

Upstream open reading frames (uORFs) are a class of translated regions (translons) in mRNA 5' leaders. uORFs are believed to be pervasive regulators of the translation of mammalian mRNAs. Some uORFs are highly repressive but others have little or no impact on downstream mRNA translation either due to inefficient recognition of their start codon(s) or/and due to efficient reinitiation after uORF translation. While experiments with uORF reporter constructs proved to be instrumental in the investigation of uORF-mediated mechanisms of translation control, they can have serious limitations as manipulations with uORF sequences can yield various artefacts. Here we propose a general approach for using translation complex profiling (TCP-seq) data for exploring uORF regulatory characteristics. Using several examples, we show how TCP-seq could be used to estimate both repressiveness and modes of action of individual uORFs. We demonstrate how this approach could be used to assess the mechanisms of uORF-mediated translation control in the mRNA of several human genes, including EIF5, IFRD1, MDM2, MIEF1, PPP1R15B, TAF7, and UCP2.

PMID:
39486574
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

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