ArticleMolecular and cellular biology2001
Dual function for U2AF(35) in AG-dependent pre-mRNA splicing.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
- REAL-TIME VISUALIZATION OF SPLICEOSOME ASSEMBLY REVEALS BASIC PRINCIPLES OF 3' SPLICE SITE SELECTION.Research square · 2026Article
- Effect of Selenium Nanoparticles on Alternative Splicing of Rainbow Trout Head Kidney under Heat Stress.Marine biotechnology (New York, N.Y.) · 2024Article
- Unearthing a novel function of SRSF1 in binding and unfolding of RNA G-quadruplexes.Nucleic acids research · 2024Article
- Global analysis of binding sites of U2AF1 and ZRSR2 reveals RNA elements required for mutually exclusive splicing by the U2- and U12-type spliceosome.Nucleic acids research · 2024Article
- Unearthing SRSF1's Novel Function in Binding and Unfolding of RNA G-Quadruplexes.bioRxiv : the preprint server for biology · 2023Article
- Cooperative engagement and subsequent selective displacement of SR proteins define the pre-mRNA 3D structural scaffold for early spliceosome assembly.Nucleic acids research · 2022Article
- Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies.Molecular cell · 2022Article
- A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2-RNA complex.Cell chemical biology · 2021Article
- Elucidation of the aberrant 3' splice site selection by cancer-associated mutations on the U2AF1.Nature communications · 2020Article
- Article
- mTOR-regulated U2af1 tandem exon splicing specifies transcriptome features for translational control.Nucleic acids research · 2019Article
- RNA Binding Motif Protein 48 Is Required for U12 Splicing and Maize Endosperm Differentiation.The Plant cell · 2019Article
- Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways.Nucleic acids research · 2017Article
- Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage.Nature communications · 2016Article
- A novel 3' splice site recognition by the two zinc fingers in the U2AF small subunit.Genes & development · 2015Article
- Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3' splice-site organization and activity of U2AF-related proteins.Nucleic acids research · 2015Article
- U2AF1 mutations alter splice site recognition in hematological malignancies.Genome research · 2015Article
- Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Article
- AG-dependent 3'-splice sites are predisposed to aberrant splicing due to a mutation at the first nucleotide of an exon.Nucleic acids research · 2011Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The splicing factor U2AF is required for the recruitment of U2 small nuclear RNP to pre-mRNAs in higher eukaryotes. The 65-kDa subunit of U2AF (U2AF(65)) binds to the polypyrimidine (Py) tract preceding the 3' splice site, while the 35-kDa subunit (U2AF(35)) contacts the conserved AG dinucleotide at the 3' end of the intron. It has been shown that the interaction between U2AF(35) and the 3' splice site AG can stabilize U2AF(65) binding to weak Py tracts characteristic of so-called AG-dependent pre-mRNAs. U2AF(35) has also been implicated in arginine-serine (RS) domain-mediated bridging interactions with splicing factors of the SR protein family bound to exonic splicing enhancers (ESE), and these interactions can also stabilize U2AF(65) binding. Complementation of the splicing activity of nuclear extracts depleted of U2AF by chromatography in oligo(dT)-cellulose requires, for some pre-mRNAs, only the presence of U2AF(65). In contrast, splicing of a mouse immunoglobulin M (IgM) M1-M2 pre-mRNA requires both U2AF subunits. In this report we have investigated the sequence elements (e.g., Py tract strength, 3' splice site AG, ESE) responsible for the U2AF(35) dependence of IgM. The results indicate that (i) the IgM substrate is an AG-dependent pre-mRNA, (ii) U2AF(35) dependence correlates with AG dependence, and (iii) the identity of the first nucleotide of exon 2 is important for U2AF(35) function. In contrast, RS domain-mediated interactions with SR proteins bound to the ESE appear to be dispensable, because the purine-rich ESE present in exon M2 is not essential for U2AF(35) activity and because a truncation mutant of U2AF(35) consisting only of the pseudo-RNA recognition motif domain and lacking the RS domain is active in our complementation assays. While some of the effects of U2AF(35) can be explained in terms of enhanced U2AF(65) binding, other activities of U2AF(35) do not correlate with increased cross-linking of U2AF(65) to the Py tract. Collectively, the results argue that interaction of U2AF(35) with a consensus 3' splice site triggers events in spliceosome assembly in addition to stabilizing U2AF(65) binding, thus revealing a dual function for U2AF(35) in pre-mRNA splicing.
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