Listening to silence and understanding nonsense: Exonic mutations that affect splicing

Nature Reviews Genetics

Volumn 3, Issue 4, 2002, Pages 285-298

  Cartegni, Luca ^a   Chew, Shern L ^b   Krainer, Adrian R ^a  

^a Howard Hughes Medical Institute Cold Spring Harbor Laboratory Cold Spring Harbor   (United States)

^b ST BARTHOLOMEW S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FIBRILLIN; MESSENGER RNA PRECURSOR;

ENHANCER REGION; EVOLUTION; EXON; GENE MUTATION; GENETIC DISORDER; HUMAN; NONHUMAN; NONSENSE MUTATION; PHENOTYPE; POINT MUTATION; PRIORITY JOURNAL; REVIEW; RNA SPLICING; RNA TRANSLATION; SILENT GENE; SINGLE NUCLEOTIDE POLYMORPHISM;

CODON, NONSENSE; ENHANCER ELEMENTS (GENETICS); EXONS; HUMANS; MUTATION, MISSENSE; NUCLEAR PROTEINS; OPEN READING FRAMES; PHENOTYPE; POINT MUTATION; RNA SPLICING; RNA, MESSENGER;

EID: 0036207384     PISSN: 14710056     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrg775     Document Type: Review

References (149)

1. Spliceosomal U snRNP biogenesis, structure and function
2. Multiple splicing defects in an intronic false exon
3. Initial sequencing and analysis of the human genome
4. The sequence of the human genome
5. Alternative splicing: Increasing diversity in the proteomic world
6. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity
7. The genome sequence of Drosophila melanogaster
8. A genomic view of alternative splicing
9. Sorting out the complexity of SR protein functions
10. Pre-mRNA splicing in the new millennium
11. Alternative splicing of pre-mRNA: Developmental consequences and mechanisms of regulation
12. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins
13. Multiple distinct splicing enhancers in the protein-coding sequences of a constitutively spliced pre-mRNA
14. Exonic splicing enhancers: Mechanism of action, diversity and role in human genetic diseases
15. Analysis of the RNA-recognition motif and RS and RGG domains: Conservation in metazoan pre-mRNA splicing factors
16. Exon definition may facilitate splice site selection in RNAs with multiple exons
17. The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing
18. The role of U2AF35 and U2AF65 in enhancer-dependent splicing
19. Pre-mRNA splicing of IgM exons M1 and M2 is directed by a juxtaposed splicing enhancer and inhibitor
20. Pre-mRNA splicing in the absence of an SR protein RS domain
21. Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins
22. Polypurine sequences within a downstream exon function as a splicing enhancer
23. A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer
24. The role of exon sequences in splice site selection
25. SR proteins promote the first specific recognition of pre-mRNA and are present together with the U1 small nuclear ribonucleoprotein particle in a general splicing enchancer complex
26. Selection of novel exon recognition elements from a pool of random sequences
27. In vitro selection of exonic splicing enhancer sequences: Identification of novel CD44 enhancers
28. Identification of a new class of exonic splicing enhancers by in vivo selection
29. Selection and characterization of pre-mRNA splicing enhancers: Identification of novel SR protein-specific enhancer sequences
30. Exonic splicing enhancer motif recognized by human SC35 under splicing conditions
31. The human splicing factors ASF/SF2 and SC35 possess distinct, functionally significant RNA binding specificities
32. Human genomic sequences that inhibit splicing
33. A novel bipartite splicing enhancer modulates the differential processing of the human fibronectin EDA exon
34. Presence of exon splicing silencers within human immunodeficiency virus type 1 tat exon 2 and tat-rev exon 3: Evidence for inhibition mediated by cellular factors
35. Identification of positive and negative splicing regulatory elements within the terminal talrev exon of human immunodeficiency virus type 1
36. A pyrimidine-rich exonic splicing suppressor binds multiple RNA splicing factors and inhibits spliceosome assembly
37. hnRNP A1 recruited to an exon in vivo can function as an exon splicing silencer
38. An exonic splicing silencer in the testes-specific DNA ligase 111β exon
39. Alternative pre-mRNA splicing: The logic of combinatorial control
40. Polypyrimidine tract binding protein antagonizes exon definition
41. hnRNP proteins and the biogenesis of mRNA
42. hnRNP complexes: Composition, structure, and function
43. Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat β-tropomyosin gene
44. Modulation of exon skipping by high-affinity hnRNP A1-binding sites and by intron elements that repress splice site utilization
45. Directing alternative splicing: Cast and scenarios
46. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: Causes and consequences
47. Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1
48. Splicing defects in the ataxia-telangiectasia gene, ATM: Underlying mutations and consequences
49. A perfect message: RNA surveillance and nonsense-mediated decay
50. When the message goes awry: Disease-producing mutations that influence mRNA content and performance
51. The skipping of constitutive exons in vivo induced by nonsense mutations
52. Maintenance of an open reading frame as an additional level of scrutiny during splice site selection
53. A premature termination codon in either exon of minute virus of mice P4 promoter-generated pre-mRNA can inhibit nuclear splicing of the intervening intron in an open reading frame-dependent manner
54. A premature termination codon interferes with the nuclear function of an exon splicing enhancer in an open reading frame-dependent manner
55. Precursor RNAs harboring nonsense codons accumulate near the site of transcription
56. Nonsense mutations in the dihydrofolate reductase gene affect RNA processing
57. When cells stop making sense: Effects of nonsense codons on RNA metabolism in vertebrate cells
58. Nonsense surveillance in lymphocytes?
59. Pre-mRNA processing: Insights from nonsense
60. Monoclonal antibody-aided characterization of cellular p220 in uninfected and poliovirus-infected HeLa cells: Subcellular distribution and identification of conformers
61. Nuclear eukaryotic initiation factor 4E (elF4E) colocalizes with splicing factors in speckles
62. Coupling of transcription and translation in Dictyostelium discoideum nuclei
63. Coupled transcription and translation within nuclei of mammalian cells
64. The structural and functional diversity of dystrophin
65. The molecular basis for Duchenne versus Becker muscular dystrophy: Correlation of severity with type of deletion
66. Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy
67. Dystrophin nonsense mutation induces different levels of exon 29 skipping and leads to variable phenotypes within one BMD family
68. Silent mutation induces exon skipping of fibrillin- 1 gene in Marian syndrome
69. Nearby stop codons in exons of the neurofibromatosis type 1 gene are disparate splice effectors
70. Predicted changes in pre-mRNA secondary structure vary in their association with exon skipping for mutations in exons 2, 4, and 8 of the Hprt gene and exon 51 of the fibrillin gene
71. The association of nonsense mutation with exon-skipping in hprt mRNA of Chinese hamster ovary cells results from an artifact of RT-PCR
72. The association of nonsense codons with exon skipping
73. Regulation of fibronectin EDA exon alternative splicing: Possible role of RNA secondary structure for enhancer display
74. A nonsense mutation and exon skipping in the Fanconi anaemia group C gene
75. Exon 6 skipping in the Fanconi anemia C gene associated with a nonsense/missense mutation (775C→T) in exon 5: The first example of a nonsense mutation in one exon causing skipping of another downstream
76. The regulation of splice-site selection, and its role in human disease
77. A BRCA1 nonsense mutation causes exon skipping
78. A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes
79. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition
80. Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene
81. IARC p53 mutation database: A relational database to compile and analyze p 53 mutations in human tumors and cell lines. International Agency for Research on Cancer
82. Identification and characterization of a spinal muscular atrophy-determining gene
83. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy
84. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2
85. An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN
86. The role of Smn in spinal muscular atrophy
87. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
88. Neurodegenerative tauopathies
89. FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10
90. Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17
91. Determinants of 4-repeat tau expression. Coordination between enhancing and inhibitory splicing sequences for exon 10 inclusion
92. Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements
93. Evidence for purifying selection acting on silent sites in BRCA1
94. Purifying selection on silent sites a constraint from splicing regulation?
95. A test of translational selection at 'silent' sites in the human genome: Base composition comparisons in alternatively spliced genes
96. The essence of SNPs
97. Characterization of single-nucleotide polymorphisms in coding regions of human genes
98. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms
99. Antisense oligonucleotides as modulators of pre-mRNA splicing
100. Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3′ splice site pairing
101. Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients
102. Treatment of spinal muscular atrophy by sodium butyrate
103. An in vivo reporter system for measuring increased inclusion of exon 7 in SMN2 mRNA: Potential therapy of SMA
104. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase
105. Engineering hybrid genes without the use of restriction enzymes: Gene splicing by overlap extension
106. In vivo SELEX in vertebrate cells
107. The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions
108. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20
109. Htra2-β1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 (SMN2)
110. The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers
111. Regulation of alternative polyadenylation by U1 snRNPs and SRp20
112. Sequence-specific RNA binding by an SR protein requires RS domain phosphorylation: Creation of an SRp40-specific splicing enhancer
113. Human Tra2 proteins are sequence-specific activators of pre-mRNA splicing
114. Adenosine deaminase deficiency in adults
115. Diverse mutations in patients with Menkes disease often lead to exon skipping
116. A missense cystic fibrosis transmembrane conductance regulator mutation with variable phenotype
117. Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621 + 3A → G, 2751 + 2T → A, 296 + 1G → C, 1717-9T → C-D565G) and one nonsense mutation (E822X) in the CFTR gene
118. Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A
119. A missense mutation (Q279R) in the fumarylacetoacetate hydrolase gene, responsible for hereditary tyrosinemia, acts as a splicing mutation
120. A single mutation that results in an Asp to His substitution and partial exon skipping in a family with congenital contractural arachnodactyly
121. Molecular characterization of a novel defect occurring de novo associated with erythropoietic protoporphyria
122. A novel exon mutation in the human β-hexosaminidase β-subunit gene affects 3′ splice site selection
123. Three splicing defects, an insertion, and two missense mutations responsible for acute intermittent porphyria
124. A G to A transition at the last nucleotide of exon 6 of the γc gene (868G →A) may result in either a splice or missense mutation in patients with X-linked severe combined immunodeficiency
125. Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene
126. Missense and nonsense mutations in codon 659 of MLH1 cause aberrant splicing of messenger RNA in HNPCC kindreds
127. Mutatons in the X-linked E1α subunit of pyruvate dehydrogenase: Exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex
128. Characterization of the 415G → A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type 1α disrupting a splicing enhancer resulting in exon 5 skipping
129. Molecular basis for Rh(null) syndrome: Identification of three new missense mutations in the Rh50 glycoprotein gene
130. A silent mutation in exon 14 of the APC gene is associated with exon skipping in a FAP family
131. A unique exonic splicing mutation in the human androgen receptor gene indicates a physiologic relevance of regular androgen receptor transcript variants
132. Silent nucleotide substitution in the sterol 27-hydroxylase gene (CYP27) leads to alternative pre-mRNA splicing by activating a cryptic 5′ splice site at the mutant codon in cerebrotendinous xanthomatosis patients
133. Hereditary tyrosinemia type 1: Novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship
134. A 'G' to 'A' mutation at position -1 of a 5′ splice site in a late infantile form of Tay-Sachs disease
135. Acute intermittent porphyria caused by defective splicing of porphobilinogen deaminase RNA: A synonymous codon mutation at 22 bp from the 5′ splice site causes skipping of exon 3
136. Glanzmann thrombasthenia. Cooperation between sequence variants in cis during splice site selection
137. Different missense mutations in histidine-108 of lysosomal acid lipase cause cholesteryl ester storage disease in unrelated compound heterozygous and hemizygous individuals
138. RNA-based mutation screening in hereditary nonpolyposis colorectal cancer
139. Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain
140. A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria
141. Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1α mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy
142. Frame shift mutation, exon skipping, and a two-codon deletion caused by splice site mutations account for pyruvate kinase deficiency
143. A point mutation in PTPRC is associated with the development of multiple sclerosis
144. Molecular characterization of 6-pyruvoyl-tetrahydropterin synthase deficiency in Japanese patients
145. Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease
146. Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM
147. Familial porphyria cutanea tarda: Characterization of seven novel uroporphynogen decarboxylase mutations and frequency of common hemochromatosis alleles