ArticlePLoS genetics2022
mRNA 5' terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and decay.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Mechanometabolism instructs hematopoietic stem cell specification.The Journal of experimental medicine · 2026Article
- Seamless, modular binary vectors for plant cell and molecular biology.Plant biotechnology journal · 2026Article
- Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs.Molecular cell · 2025Article
- Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations.Nature communications · 2024Article
- Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs.Science advances · 2024Article
- Intra-promoter switch of transcription initiation sites in proliferation signaling-dependent RNA metabolism.Nature structural & molecular biology · 2023Article
- Conserved Functions of LARP1 Proteins in Eukaryotes.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
mRNA regulatory sequences control gene expression at multiple levels including translation initiation and mRNA decay. The 5' terminal sequences of mRNAs have unique regulatory potential because of their proximity to key post-transcriptional regulators. Here we have systematically probed the function of 5' terminal sequences in gene expression in human cells. Using a library of reporter mRNAs initiating with all possible 7-mer sequences at their 5' ends, we find an unexpected impact on transcription that underlies 200-fold differences in mRNA expression. Library sequences that promote high levels of transcription mirrored those found in native mRNAs and define two basic classes with similarities to classic Initiator (Inr) and TCT core promoter motifs. By comparing transcription, translation and decay rates, we identify sequences that are optimized for both efficient transcription and growth-regulated translation and stability, including variants of terminal oligopyrimidine (TOP) motifs. We further show that 5' sequences of endogenous mRNAs are enriched for multi-functional TCT/TOP hybrid sequences. Together, our results reveal how 5' sequences define two general classes of mRNAs with distinct growth-responsive profiles of expression across synthesis, translation and decay.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.