Home LiteratureArticle Details
PMID: 7567473 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Relative exon affinities and suboptimal splice site signals lead to non-equivalence of two cassette exons.

Nucleic acids research ·Vol. 23 ·No. 17 ·1995-09-11 ·Pages 3585-93

Andreadis A, Broderick JA, Kosik KS

Abstract

Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exons 2 and 3 of the gene are alternatively spliced cassettes in which exon 3 never appears independently of exon 2. Expression of tau minigene constructs in cells indicate that exon 2 resembles a constitutive exon, while a suboptimal branch point connected to exon 3 inhibits inclusion of exon 3 in the mRNA. Splicing of the two tau exons is controlled by their relative affinities for each other versus the affinities of their flanking exons for them.

MeSH Terms
Alternative Splicing Animals Base Sequence Chlorocebus aethiops Exons Gene Expression Humans In Vitro Techniques Molecular Sequence Data RNA Precursors/metabolism RNA, Messenger/genetics Structure-Activity Relationship Tumor Cells, Cultured tau Proteins/genetics
Chemicals
RNA Precursors RNA, Messenger tau Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Andreadis A
Department of Neurology (Neuroscience), Harvard Medical School, Boston, MA, USA.
Broderick J A
Kosik K S
References (50)
50 references, click to expand
  1. Scanning and competition between AGs are involved in 3' splice site selection in mammalian introns.
    Mol Cell Biol. 1993 Aug;13(8):4939-52 PMID: 8336728
  2. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease.
    Neuron. 1989 Oct;3(4):519-26 PMID: 2484340
  3. Generation of protein isoform diversity by alternative splicing: mechanistic and biological implications.
    Annu Rev Cell Biol. 1987;3:207-42 PMID: 2891362
  4. The role of exon sequences in splice site selection.
    Genes Dev. 1993 Mar;7(3):407-18 PMID: 8449402
  5. Structure and novel exons of the human tau gene.
    Biochemistry. 1992 Nov 3;31(43):10626-33 PMID: 1420178
  6. A new cationic liposome reagent mediating nearly quantitative transfection of animal cells.
    Biotechniques. 1991 Apr;10(4):520-5 PMID: 1867862
  7. Effect of 5' splice site mutations on splicing of the preceding intron.
    Mol Cell Biol. 1990 Dec;10(12):6299-305 PMID: 2247057
  8. Heterogeneity of tau proteins in Alzheimer's disease. Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites.
    Am J Pathol. 1993 Feb;142(2):387-94 PMID: 7679548
  9. Developmentally regulated expression of specific tau sequences.
    Neuron. 1989 Apr;2(4):1389-97 PMID: 2560640
  10. Selection of splice sites in pre-mRNAs with short internal exons.
    Mol Cell Biol. 1991 Dec;11(12):6075-83 PMID: 1944277
  11. Mutually exclusive splicing of alpha-tropomyosin exons enforced by an unusual lariat branch point location: implications for constitutive splicing.
    Cell. 1989 Mar 10;56(5):749-58 PMID: 2924347
  12. Alternative splicing of tropomyosin pre-mRNAs in vitro and in vivo.
    Genes Dev. 1988 Dec;2(12A):1627-38 PMID: 3215513
  13. Does steric interference between splice sites block the splicing of a short c-src neuron-specific exon in non-neuronal cells?
    Genes Dev. 1991 Mar;5(3):389-402 PMID: 2001841
  14. Expression of beta amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer's disease using PCR.
    Neuron. 1990 Feb;4(2):253-67 PMID: 2106330
  15. Identification of a novel neuronal C-SRC exon expressed in human brain.
    Mol Cell Biol. 1990 May;10(5):2035-40 PMID: 1691439
  16. Alternative splicing of beta-tropomyosin pre-mRNA: cis-acting elements and cellular factors that block the use of a skeletal muscle exon in nonmuscle cells.
    Genes Dev. 1991 Nov;5(11):2096-107 PMID: 1936995
  17. Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element.
    Genes Dev. 1994 Jul 1;8(13):1561-74 PMID: 7958840
  18. Microtubule-bundling studies revisited: is there a role for MAPs?
    Trends Cell Biol. 1992 Oct;2(10):286-9 PMID: 14731912
  19. Scanning from an independently specified branch point defines the 3' splice site of mammalian introns.
    Nature. 1989 Nov 16;342(6247):243-7 PMID: 2812024
  20. Alpha-tropomyosin mutually exclusive exon selection: competition between branchpoint/polypyrimidine tracts determines default exon choice.
    Genes Dev. 1991 Apr;5(4):642-55 PMID: 2010089
  21. Splicing of SV40 early pre-mRNA to large T and small t mRNAs utilizes different patterns of lariat branch sites.
    Cell. 1987 Jul 17;50(2):227-36 PMID: 3036371
  22. Elements regulating an alternatively spliced exon of the rat fibronectin gene.
    Mol Cell Biol. 1993 Sep;13(9):5301-14 PMID: 8355683
  23. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  24. Casein kinase II preferentially phosphorylates human tau isoforms containing an amino-terminal insert. Identification of threonine 39 as the primary phosphate acceptor.
    J Biol Chem. 1994 Feb 11;269(6):4373-80 PMID: 8308007
  25. Tau protein: an update on structure and function.
    Cell Motil Cytoskeleton. 1990;15(4):199-203 PMID: 2110865
  26. The 216-nucleotide intron of the E1A pre-mRNA contains a hairpin structure that permits utilization of unusually distant branch acceptors.
    Mol Cell Biol. 1989 Nov;9(11):4852-61 PMID: 2601698
  27. A sequence compilation and comparison of exons that are alternatively spliced in neurons.
    Nucleic Acids Res. 1994 May 11;22(9):1515-26 PMID: 8202349
  28. Branch point selection in alternative splicing of tropomyosin pre-mRNAs.
    Nucleic Acids Res. 1989 Jul 25;17(14):5633-50 PMID: 2762151
  29. Alternative splicing of SV40 early pre-mRNA is determined by branch site selection.
    Genes Dev. 1988 Nov;2(11):1460-75 PMID: 2850262
  30. Primary structure of high molecular weight tau present in the peripheral nervous system.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4378-81 PMID: 1374898
  31. Microtubule-associated proteins: their potential role in determining neuronal morphology.
    Annu Rev Neurosci. 1988;11:29-44 PMID: 3284444
  32. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  33. In vivo recognition of a vertebrate mini-exon as an exon-intron-exon unit.
    Mol Cell Biol. 1993 May;13(5):2677-87 PMID: 7682652
  34. Control of calcitonin/calcitonin gene-related peptide pre-mRNA processing by constitutive intron and exon elements.
    Mol Cell Biol. 1993 Oct;13(10):5999-6011 PMID: 8413203
  35. Tau consists of a set of proteins with repeated C-terminal microtubule-binding domains and variable N-terminal domains.
    Mol Cell Biol. 1989 Apr;9(4):1381-8 PMID: 2498649
  36. Exon definition may facilitate splice site selection in RNAs with multiple exons.
    Mol Cell Biol. 1990 Jan;10(1):84-94 PMID: 2136768
  37. The exon trapping assay partly discriminates against alternatively spliced exons.
    Nucleic Acids Res. 1993 May 11;21(9):2217-21 PMID: 7684835
  38. The role of the mammalian branchpoint sequence in pre-mRNA splicing.
    Genes Dev. 1988 Oct;2(10):1268-76 PMID: 3060403
  39. Alternative splicing in the neural cell adhesion molecule pre-mRNA: regulation of exon 18 skipping depends on the 5'-splice site.
    Genes Dev. 1991 Aug;5(8):1416-29 PMID: 1869048
  40. Myosin light-chain 1/3 gene alternative splicing: cis regulation is based upon a hierarchical compatibility between splice sites.
    Mol Cell Biol. 1990 May;10(5):2133-44 PMID: 2325649
  41. Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing.
    Nucleic Acids Res. 1989 Oct 11;17(19):7905-21 PMID: 2798134
  42. Biochemical mechanisms of constitutive and regulated pre-mRNA splicing.
    Annu Rev Cell Biol. 1991;7:559-99 PMID: 1839712
  43. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination.
    Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963-5 PMID: 6575390
  44. Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system.
    Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1983-7 PMID: 1542696
  45. Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro.
    Cell. 1992 May 29;69(5):795-807 PMID: 1591778
  46. Cooperation of pre-mRNA sequence elements in splice site selection.
    Mol Cell Biol. 1992 May;12(5):2108-14 PMID: 1569943
  47. In vivo splicing of the beta tropomyosin pre-mRNA: a role for branch point and donor site competition.
    Mol Cell Biol. 1992 Jul;12(7):3204-15 PMID: 1620126
  48. Combinatorial splicing of exon pairs by two-site binding of U1 small nuclear ribonucleoprotein particle.
    Mol Cell Biol. 1991 Dec;11(12):5919-28 PMID: 1834932
  49. The cardiac troponin T alternative exon contains a novel purine-rich positive splicing element.
    Mol Cell Biol. 1993 Jun;13(6):3660-74 PMID: 8388541
  50. Split genes and RNA splicing.
    Cell. 1994 Jun 17;77(6):805-15 PMID: 7516265
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/23.17.3585
Published
1995-09-11
Pages
3585-93
Language
English
Region
England
NLM ID
0411011
PMCID
PMC307241
Subset
IM
Grants
NIA NIH HHS · AG06601 · United States
Databases
GENBANK
L35768, L35769
External Links
PubMed source DOI: 10.1093/nar/23.17.3585 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2