ArticleGenome research2019
A massively parallel 3' UTR reporter assay reveals relationships between nucleotide content, sequence conservation, and mRNA destabilization.
Article in Genome research, 2019. 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, 63 citations in OpenAlex.
- From RNA design to delivery: Computational strategies for functional RNA therapeutics.Bioactive materials · 2027Review
- Structural variation in the IAMH2 3' UTR underlies hypocotyl elongation during light adaptation in Arabidopsis thaliana.The Plant journal : for cell and molecular biology · 2026Article
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- Intermolecular 3'UTR-3'UTR interactions drive Wnt gene activation through heteromeric protein assembly.bioRxiv : the preprint server for biology · 2026Article
- The quantitative impact of 3'UTRs on gene expression.Nucleic acids research · 2025Article
- Article
- mRNA vaccine sequence and structure design and optimization: Advances and challenges.The Journal of biological chemistry · 2025Review
- NaP-TRAP reveals the regulatory grammar in 5'UTR-mediated translation regulation during zebrafish development.Nature communications · 2024Article
- Long-read subcellular fractionation and sequencing reveals the translational fate of full-length mRNA isoforms during neuronal differentiation.Genome research · 2024Article
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- A new perspective on microRNA-guided gene regulation specificity, and its potential generalization to transcription factors and RNA-binding proteins.Nucleic acids research · 2024Review
- Review
- Predicting functional UTR variants by integrating region-specific features.Briefings in bioinformatics · 2024Article
- Determinants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci.Nature communications · 2024Article
- UPF1 regulates mRNA stability by sensing poorly translated coding sequences.Cell reports · 2024Article
- A Cre-dependent massively parallel reporter assay allows for cell-type specific assessment of the functional effects of non-coding elements in vivo.Communications biology · 2023Article
- Review
- Multi-level functional genomics reveals molecular and cellular oncogenicity of patient-based 3' untranslated region mutations.Cell reports · 2023Article
- The long and short of EJC-independent nonsense-mediated RNA decay.Biochemical Society transactions · 2023Review
- Cumulative effects of weakly repressive regulatory regions in the 3' UTR maintain PD-1 expression homeostasis in mammals.Communications biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Compared to coding sequences, untranslated regions of the transcriptome are not well conserved, and functional annotation of these sequences is challenging. Global relationships between nucleotide composition of 3' UTR sequences and their sequence conservation have been appreciated since mammalian genomes were first sequenced, but the functional relevance of these patterns remain unknown. We systematically measured the effect on gene expression of the sequences of more than 25,000 RNA-binding protein (RBP) binding sites in primary mouse T cells using a massively parallel reporter assay. GC-rich sequences were destabilizing of reporter mRNAs and come from more rapidly evolving regions of the genome. These sequences were more likely to be folded in vivo and contain a number of structural motifs that reduced accumulation of a heterologous reporter protein. Comparison of full-length 3' UTR sequences across vertebrate phylogeny revealed that strictly conserved 3' UTRs were GC-poor and enriched in genes associated with organismal development. In contrast, rapidly evolving 3' UTRs tended to be GC-rich and derived from genes involved in metabolism and immune responses. Cell-essential genes had lower GC content in their 3' UTRs, suggesting a connection between unstructured mRNA noncoding sequences and optimal protein production. By reducing gene expression, GC-rich RBP-occupied sequences act as a rapidly evolving substrate for gene regulatory interactions.
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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.