ArticleNucleic acids research1998
Efficient 3'-end formation of human beta-globin mRNA in vivo requires sequences within the last intron but occurs independently of the splicing reaction.
Article in Nucleic acids research, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Structure-guided engineering of prototype foamy virus Env identifies key residues for heparan sulfate binding and enhances transduction efficiency.Frontiers in bioengineering and biotechnology · 2026Article
- The regulation and function of post-transcriptional RNA splicing.Nature reviews. Genetics · 2025Review
- A differentiated β-globin gene replacement strategy uses heterologous introns to restore physiological expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Human RNA Polymerase II Segregates from Genes and Nascent RNA and Transcribes in the Presence of DNA-Bound dCas9.International journal of molecular sciences · 2024Article
- The polyA tail facilitates splicing of last introns with weak 3' splice sites via PABPN1.EMBO reports · 2023Article
- Introns and Their Therapeutic Applications in Biomedical Researches.Iranian journal of biotechnology · 2023Review
- Article
- Pre-mRNA splicing and its cotranscriptional connections.Trends in genetics : TIG · 2023Review
- Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies.Molecular therapy. Nucleic acids · 2023Article
- Gene modification therapies for hereditary diseases in the fetus.Prenatal diagnosis · 2023Review
- Co-transcriptional splicing regulates 3' end cleavage during mammalian erythropoiesis.Molecular cell · 2021Article
- Proximity to the Promoter and Terminator Regions Regulates the Transcription Enhancement Potential of an Intron.Frontiers in molecular biosciences · 2021Article
- Sequence determinants of polyadenylation-mediated regulation.Genome research · 2019Article
- A comparison of intrauterine hemopoietic cell transplantation and lentiviral gene transfer for the correction of severe β-thalassemia in a HbbTh3/+ murine model.Experimental hematology · 2018Article
- Identification of introns harboring functional sequence elements through positional conservation.Scientific reports · 2017Article
- Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA.PLoS genetics · 2017Article
- Introns: The Functional Benefits of Introns in Genomes.Genomics & informatics · 2015Review
- Long-term and efficient expression of human β-globin gene in a hematopoietic cell line using a new site-specific integrating non-viral system.Gene therapy · 2015Article
- The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.Molecular therapy. Methods & clinical development · 2015Article
- Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two partially redundant degradation pathways.RNA (New York, N.Y.) · 2013Article
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4 authors.
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Abstract
The second intron (betaIVS-II) of the human beta-globin gene is essential for the accumulation of stable cytoplasmic mRNA and is implicated in promoting efficient 3'-end formation. This report presents quantitative comparisons between betaIVS-II mutants at physiological levels of expression from within a natural chromatin context in vivo which further defines it's function. In marked contrast to a beta-globin gene lacking a second intron, two mutants defective in splicing (small size or a splice donor mutation), still undergo essentially normal levels of 3'-end formation and in the absence of exon skipping. Therefore, 3' cleavage of beta-globin transcripts requires the presence of betaIVS-II sequences, but not the splicing reaction. The placement of betaIVS-II in the IVS-I position did not reduce the efficiency of 3' cleavage indicating that the distance between the necessary element(s) in this intron and the polyadenylation recognition site is not a crucial factor. Subsequent placement of betaIVS-I in the intron II position, reduced the efficiency of 3'-end formation to only 16% of normal. A direct replacement of intron II by the heterologous introns betaIVS-I or alpha-globin IVS-II, only partially substitute (16 and 30% respectively) for betaIVS-II. Hybrid introns show that efficient 3'-end formation is strongly enhanced by the presence of the terminal 60 nt of betaIVS-II. These data imply that the last intervening sequence of multiple intron containing genes is a principal determinant of the efficiency of 3'-end formation and may act as a post-transcriptional regulatory step in gene expression.
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