ArticlePLoS genetics2015
Systematic dissection of the sequence determinants of gene 3' end mediated expression control.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 72 citations in OpenAlex.
- Leveraging pre-trained AI models for robust promoter sequence design in synthetic biology.Biophysics reports · 2026Article
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- Chromatin regulates alternative polyadenylation via the RNA polymerase II elongation rate.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Species-aware DNA language models capture regulatory elements and their evolution.Genome biology · 2024Article
- Stress responses of plants through transcriptome plasticity by mRNA alternative polyadenylation.Molecular horticulture · 2023Review
- Controlling gene expression with deep generative design of regulatory DNA.Nature communications · 2022Article
- Article
- Effects of sequence motifs in the yeast 3' untranslated region determined from massively parallel assays of random sequences.Genome biology · 2021Article
- Article
- A broad analysis of splicing regulation in yeast using a large library of synthetic introns.PLoS genetics · 2021Article
- Learning the Regulatory Code of Gene Expression.Frontiers in molecular biosciences · 2021Review
- Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure.Nature communications · 2020Article
- Article
- Systematic identification ofeLife · 2020Article
- Development of a species-specific transformation system using the novel endogenous promoter calreticulin from oleaginous microalgae Ettlia sp.Scientific reports · 2020Article
- Deciphering eukaryotic gene-regulatory logic with 100 million random promoters.Nature biotechnology · 2020Article
- MaveDB: an open-source platform to distribute and interpret data from multiplexed assays of variant effect.Genome biology · 2019Article
- Sequence determinants of polyadenylation-mediated regulation.Genome research · 2019Article
- Functional assays for transcription mechanisms in high-throughput.Methods (San Diego, Calif.) · 2019Review
- Systematic interrogation of human promoters.Genome research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 3'end genomic region encodes a wide range of regulatory process including mRNA stability, 3' end processing and translation. Here, we systematically investigate the sequence determinants of 3' end mediated expression control by measuring the effect of 13,000 designed 3' end sequence variants on constitutive expression levels in yeast. By including a high resolution scanning mutagenesis of more than 200 native 3' end sequences in this designed set, we found that most mutations had only a mild effect on expression, and that the vast majority (~90%) of strongly effecting mutations localized to a single positive TA-rich element, similar to a previously described 3' end processing efficiency element, and resulted in up to ten-fold decrease in expression. Measurements of 3' UTR lengths revealed that these mutations result in mRNAs with aberrantly long 3'UTRs, confirming the role for this element in 3' end processing. Interestingly, we found that other sequence elements that were previously described in the literature to be part of the polyadenylation signal had a minor effect on expression. We further characterize the sequence specificities of the TA-rich element using additional synthetic 3' end sequences and show that its activity is sensitive to single base pair mutations and strongly depends on the A/T content of the surrounding sequences. Finally, using a computational model, we show that the strength of this element in native 3' end sequences can explain some of their measured expression variability (R = 0.41). Together, our results emphasize the importance of efficient 3' end processing for endogenous protein levels and contribute to an improved understanding of the sequence elements involved in this process.
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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.