A moveable 5' splice site in adenine phosphoribosyltransferase genes of Drosophila species

1989 ◽  
Vol 9 (5) ◽  
pp. 2220-2223
Author(s):  
D Johnson ◽  
S Henikoff
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Splice Site ◽  
Gene Evolution ◽  
Drosophila Species ◽  
Splice Sites ◽  
Adenine Phosphoribosyltransferase ◽  
Splice Junctions ◽  
Encoding Genes ◽  
Normal Feature

In two distantly related Drosophila species, the use of alternate 5' splice sites to process an intron in pre-mRNA from homologous adenine phosphoribosyltransferase (APRT)-encoding genes led to RNAs encoding nonfunctional peptides in addition to APRT. The production of aberrantly spliced transcripts as a normal feature of gene expression supports a general model of eucaryotic gene evolution through alternative splicing and moveable splice junctions.

scholarly journals A moveable 5' splice site in adenine phosphoribosyltransferase genes of Drosophila species.

1989 ◽  
Vol 9 (5) ◽  
pp. 2220-2223 ◽  
Author(s):  
D Johnson ◽  
S Henikoff
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Splice Site ◽  
Gene Evolution ◽  
Drosophila Species ◽  
Splice Sites ◽  
Adenine Phosphoribosyltransferase ◽  
Splice Junctions ◽  
Encoding Genes ◽  
Normal Feature

In two distantly related Drosophila species, the use of alternate 5' splice sites to process an intron in pre-mRNA from homologous adenine phosphoribosyltransferase (APRT)-encoding genes led to RNAs encoding nonfunctional peptides in addition to APRT. The production of aberrantly spliced transcripts as a normal feature of gene expression supports a general model of eucaryotic gene evolution through alternative splicing and moveable splice junctions.

scholarly journals hnRNP A1 Regulates Alternative Splicing of Tau Exon 10 by Targeting 3′ Splice Sites

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 936 ◽  
Author(s):  
Yongchao Liu ◽  
Donggun Kim ◽  
Namjeong Choi ◽  
Jagyeong Oh ◽  
Jiyeon Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Alternative Splicing ◽  
Splice Site ◽  
Hnrnp A1 ◽  
Gene Ontology Analysis ◽  
Splice Sites ◽  
Neuronal Function ◽  
Brain Functions ◽  
Exon 10

The ratio control of 4R-Tau/3R-Tau by alternative splicing of Tau exon 10 is important for maintaining brain functions. In this study, we show that hnRNP A1 knockdown induces inclusion of endogenous Tau exon 10, conversely, overexpression of hnRNP A1 promotes exon 10 skipping of Tau. In addition, hnRNP A1 inhibits splicing of intron 9, but not intron 10. Furthermore, hnRNP A1 directly interacts with the 3′ splice site of exon 10 to regulate its functions in alternative splicing. Finally, gene ontology analysis demonstrates that hnRNP A1-induced splicing and gene expression targets a subset of genes with neuronal function.

scholarly journals Sequence determinants and evolution of constitutive and alternative splicing in yeast species

2020 ◽  
Author(s):  
Dvir Schirman ◽  
Zohar Yakhini ◽  
Orna Dahan ◽  
Yitzhak Pilpel
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Splice Site ◽  
Rna Splicing ◽  
Yeast Species ◽  
Combinatorial Design ◽  
Splice Sites ◽  
Eukaryotic Gene ◽  
Splicing Efficiency ◽  
Splicing Machinery

RNA splicing is a key process in eukaryotic gene expression. Most Intron-containing genes are constitutively spliced, hence efficient splicing of an intron is crucial for efficient gene expression. Here we use a large synthetic oligo library of ~20,000 variants to explore how different intronic sequence features affect splicing efficiency and mRNA expression levels in S. cerevisiae. Using a combinatorial design of synthetic introns we demonstrate how non-consensus splice site sequences affect splicing efficiency in each of the three splice sites. We then show that S. cerevisiae splicing machinery tends to select alternative 3' splice sites downstream of the original site, and we suggest that this tendency created a selective pressure, leading to the avoidance of cryptic splice site motifs near introns' 3' ends. We further use natural intronic sequences from other yeast species, whose splicing machineries have diverged to various extents, to show how intron architectures in the various species have been adapted to the organism's splicing machinery. We suggest that the observed tendency for cryptic splicing is a result of a loss of a specific splicing factor, U2AF1. Lastly, we show that synthetic sequences containing two introns give rise to alternative RNA isoforms in S. cerevisiae, exposing intronic features that control and facilitate alternative splicing. Our study reveals novel mechanisms by which introns are shaped in evolution to allow cells to regulate their transcriptome.

scholarly journals Animal, fungi, and plant genome sequences harbour different non-canonical splice sites

2019 ◽  
Author(s):  
Katharina Frey ◽  
Boas Pucker
Keyword(s):  
Splice Site ◽  
Plant Genome ◽  
Fungal Genome ◽  
Rna Seq ◽  
Splice Sites ◽  
Genome Sequences ◽  
Oikopleura Dioica ◽  
Protein Encoding ◽  
Encoding Genes ◽  
Splice Site Usage

AbstractMost protein encoding genes in eukaryotes contain introns which are interwoven with exons. After transcription, introns need to be removed in order to generate the final mRNA which can be translated into an amino acid sequence. Precise excision of introns by the spliceosome requires conserved dinucleotides which mark the splice sites. However, there are variations of the highly conserved combination of GT at the 5’ end and AG at the 3’ end of an intron in the genome. GC-AG and AT-AC are two major non-canonical splice site combinations which have been known for years. During the last years, various minor non-canonical splice site combinations were detected with numerous dinucleotide permutations. Here we expand systematic investigations of non-canonical splice site combinations in plants to all eukaryotes by analysing fungal and animal genome sequences. Comparisons of splice site combinations between these three kingdoms revealed several differences such as a substantially increased CT-AC frequency in fungal genome sequences. Canonical GT-AG splice site combinations in antisense transcripts could be one explanation for this observation. In addition, high numbers of GA-AG splice site combinations were observed in Eurytemora affinis and Oikopleura dioica. A variant in one U1 snRNA isoform might allow the recognition of GA as 5’ splice site. In depth investigation of splice site usage based on RNA-Seq read mappings indicates a generally higher flexibility of the 3’ splice site compared to the 5’ splice site across animals, fungi, and plants.

scholarly journals Combinatorial Control of Exon Recognition

2007 ◽  
Vol 283 (3) ◽  
pp. 1211-1215 ◽  
Author(s):  
Klemens J. Hertel
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Cell Types ◽  
Splice Sites ◽  
Splice Site Selection ◽  
Multiple Parameters ◽  
Splicing Regulators ◽  
Eukaryotic Genes ◽  
Different Cell Types ◽  
Mature Mrnas

Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome, which catalyzes the removal of noncoding intronic sequences to assemble exons into mature mRNAs prior to export and translation. Given the complexity of higher eukaryotic genes and the relatively low level of splice site conservation, the precision of the splicing machinery in recognizing and pairing splice sites is impressive. Introns ranging in size from <100 up to 100,000 bases are removed efficiently. At the same time, a large number of alternative splicing events are observed between different cell types, during development, or during other biological processes. This extensive alternative splicing implies a significant flexibility of the spliceosome to identify and process exons within a given pre-mRNA. To reach this flexibility, splice site selection in higher eukaryotes has evolved to depend on multiple parameters such as splice site strength, the presence or absence of splicing regulators, RNA secondary structures, the exon/intron architecture, and the process of pre-mRNA synthesis itself. The relative contributions of each of these parameters control how efficiently splice sites are recognized and flanking introns are removed.

Factor interactions with the simian virus 40 early pre-mRNA influence branch site selection and alternative splicing

1989 ◽  
Vol 9 (5) ◽  
pp. 2007-2017
Author(s):  
J C Noble ◽  
H Ge ◽  
M Chaudhuri ◽  
J L Manley
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Rnase Protection Assay ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Splice Sites ◽  
Rnase Protection ◽  
Branch Site ◽  
Factor Interactions ◽  
Selection Of

To study the interaction of splicing factors with the simian virus 40 early-region pre-RNA, which can be alternatively spliced to produce large T and small t mRNAs, we used an in vitro RNase protection assay that defines the 5' boundaries of factor-RNA interactions. Protection products reflecting factor interactions with the large T and small t 5' splice sites and with the multiple lariat branch site region were characterized. All protection products were detected very early in the splicing reaction, before the appearance of spliced RNAs. However, protection of the large T 5' splice site was detected well before small t 5' splice site and branch site protection products, which appeared simultaneously. Oligonucleotide-targeted degradation of small nuclear RNAs (snRNAs) revealed that protection of the branch site region, which occurred at multiple sites, required intact U2 snRNA and was enhanced by U1 snRNA, while protection of the large T and small t 5' splice sites required both U1 and U2 snRNAs. Analysis of several pre-RNAs containing mutations in the branch site region suggests that factor interactions involving the multiple copies of the branch site consensus determine the selection of branch points, which is an important factor in the selection of alternative splicing pathways.

scholarly journals Finding a possible biomarker to tackle Parkinson’s disease by splice analysis and random point mutations to counter the expression of genes involved in Parkinson’s disease

2017 ◽  
Vol 5 (3) ◽  
pp. 336-344
Author(s):  
Piyusha Kalwad ◽  
Ranjitha Guttapadu ◽  
Pradeep S
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alternative Splicing ◽  
Splice Site ◽  
Point Mutations ◽  
Random Point ◽  
Site Analysis ◽  
High Effect ◽  
Expression Of Genes

The genes showing aberrant alternative splicing in Parkinson’s disease namely SNCA, SNCAIP, LRRK2, SRRM2, MAPT and PARK2 were analysed. Two of the genes, namely SNCAIP and SRRM2 that showed high effect were taken and splice site analysis was carried out. Random mutations were carried out on these two genes using Human Splicing Finder tool and the mutations showing the most promising results (i.e., mutations that can restore natural gene expression) were appropriately chosen to tackle Parkinson’s disease.Int. J. Appl. Sci. Biotechnol. Vol 5(3): 336-344

scholarly journals Prp8 impacts cryptic but not alternative splicing frequency

2019 ◽  
Vol 116 (6) ◽  
pp. 2193-2199 ◽  
Author(s):  
Megan Mayerle ◽  
Samira Yitiz ◽  
Cameron Soulette ◽  
Lucero E. Rogel ◽  
Andrea Ramirez ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Hereditary Diseases ◽  
Splice Sites ◽  
Catalytic Core ◽  
C Elegans ◽  
Cellular Factors ◽  
The Stability ◽  
Cryptic Splice Sites ◽  
Splicing Patterns

Pre-mRNA splicing must occur with extremely high fidelity. Spliceosomes assemble onto pre-mRNA guided by specific sequences (5′ splice site, 3′ splice site, and branchpoint). When splice sites are mutated, as in many hereditary diseases, the spliceosome can aberrantly select nearby pseudo- or “cryptic” splice sites, often resulting in nonfunctional protein. How the spliceosome distinguishes authentic splice sites from cryptic splice sites is poorly understood. We performed aCaenorhabditis elegansgenetic screen to find cellular factors that affect the frequency with which the spliceosome uses cryptic splice sites and identified two alleles in core spliceosome component Prp8 that alter cryptic splicing frequency. Subsequent complementary genetic and structural analyses in yeast implicate these alleles in the stability of the spliceosome’s catalytic core. However, despite a clear effect on cryptic splicing, high-throughput mRNA sequencing of theseprp-8mutantC. elegansreveals that overall alternative splicing patterns are relatively unchanged. Our data suggest the spliceosome evolved intrinsic mechanisms to reduce the occurrence of cryptic splicing and that these mechanisms are distinct from those that impact alternative splicing.

scholarly journals Regulated splicing of the Drosophila sex-lethal male exon involves a blockage mechanism.

1993 ◽  
Vol 13 (3) ◽  
pp. 1408-1414 ◽  
Author(s):  
J I Horabin ◽  
P Schedl
Keyword(s):  
Drosophila Melanogaster ◽  
Alternative Splicing ◽  
Sex Determination ◽  
Splice Site ◽  
Feedback Loop ◽  
Splice Sites ◽  
Alternate Splicing ◽  
Sequence Context ◽  
Sex Lethal ◽  
Hodgkin Cell

In Drosophila melanogaster, sex determination in somatic cells is controlled by a cascade of genes whose expression is regulated by alternative splicing [B. S. Baker, Nature (London) 340:521-524, 1989; J. Hodgkin, Cell 56:905-906, 1989]. The master switch gene in this hierarchy is Sex-lethal. Sex-lethal is turned on only in females, and an autoregulatory feedback loop which controls alternative splicing maintains this state (L. R. Bell, J. I. Horabin, P. Schedl, and T. W. Cline, Cell 65:229-239, 1991; L. N. Keyes, T. W. Cline, and P. Schedl, Cell 68:933-943, 1992). Sex-lethal also promotes female differentiation by controlling the splicing of RNA from the next gene in the hierarchy, transformer. Sosnowski et al. (B. A. Sosnowski, J. M. Belote, and M. McKeown, Cell 58:449-459, 1989) have shown that the mechanism for generating female transformer transcripts is not through the activation of the alternative splice site but by the blockage of the default splice site. We have tested whether an activation or a blockage mechanism is involved in Sex-lethal autoregulation. The male exon of Sex-lethal with flanking splice sites was placed into the introns of heterologous genes. Our results support the blockage mechanism. The poly(U) run at the male exon 3' splice site is required for sex-specific splicing. However, unlike transformer, default splicing to the male exon is sensitive to the sequence context within which the exon resides. This and the observation that the splice signals at the exon are suboptimal are discussed with regard to alternate splicing.

scholarly journals The exon junction complex and intron removal prevent re-splicing of mRNA

PLoS Genetics ◽  
2021 ◽  
Vol 17 (5) ◽  
pp. e1009563
Author(s):  
Brian Joseph ◽  
Eric C. Lai
Keyword(s):  
Gene Expression ◽  
Splice Site ◽  
Site Selection ◽  
Exon Junction Complex ◽  
Splice Sites ◽  
Splice Site Selection ◽  
Exon Junction ◽  
Intron Removal ◽  
Cryptic Splice Sites

Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, splice sites (SS). However, the evolutionary generality of this remains unclear. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cryptic SS, even though most bear weak splicing motifs and are seemingly incompetent. Mechanistically, the EJC directly conceals cryptic splicing elements by virtue of its position-specific recruitment, preventing aberrant SS definition. Unexpectedly, we discover the EJC inhibits scores of regenerated 5’ and 3’ recursive SS on segments that have already undergone splicing, and that loss of EJC regulation triggers faulty resplicing of mRNA. An important corollary is that certain intronless cDNA constructs yield unanticipated, truncated transcripts generated by resplicing. We conclude the EJC has conserved roles to defend transcriptome fidelity by (1) repressing illegitimate splice sites on pre-mRNAs, and (2) preventing inadvertent activation of such sites on spliced segments.

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