Functional splice sites in a zebrafish LINE and their influence on zebrafish gene expression

Gene ◽  
2007 ◽  
Vol 390 (1-2) ◽  
pp. 221-231 ◽  
Author(s):  
Masato Tamura ◽  
Masaki Kajikawa ◽  
Norihiro Okada
Keyword(s):  
Gene Expression ◽  
Splice Sites

Role of small nuclear RNAs in eukaryotic gene expression

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Stability ◽  
Splice Sites ◽  
Branch Site ◽  
Small Nuclear Rnas ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

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 Activity of the Human Papillomavirus Type 16 Late Negative Regulatory Element Is Partly due to Four Weak Consensus 5′ Splice Sites That Bind a U1 snRNP-Like Complex

2003 ◽  
Vol 77 (9) ◽  
pp. 5167-5177 ◽  
Author(s):  
Sarah A. Cumming ◽  
Maria G. McPhillips ◽  
Thanaporn Veerapraditsin ◽  
Steven G. Milligan ◽  
Sheila V. Graham
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Epithelial Cells ◽  
Regulatory Element ◽  
Splice Sites ◽  
Hpv 16 ◽  
Negative Regulatory Element ◽  
Differentiated Cells ◽  
U1 Snrnp ◽  
Basal Epithelial Cells

ABSTRACT The human papillomavirus (HPV) life cycle is tightly linked to differentiation of the squamous epithelia that it infects. Capsid proteins, and hence mature virions, are produced in the outermost layer of differentiated cells. As late gene transcripts are produced in the lower layers, posttranscriptional mechanisms likely prevent capsid protein production in less differentiated cells. For HPV type 16 (HPV-16), a 79-nucleotide (nt) negative regulatory element (NRE) inhibits gene expression in basal epithelial cells. To identify key NRE sequences, we carried out transient transfection in basal epithelial cells with reporter constructs containing the HPV-16 late 3′ untranslated region with deletions and mutations of the NRE. Reporter gene expression was increased over 40-fold by deletion of the entire element, 10-fold by deletion of the 5′ portion of the NRE that contains four weak consensus 5′ splice sites, and only 3-fold by deletion of the 3′ GU-rich region. Both portions of the element appear to be necessary for full repression. Inactivating mutations in the 5′ splice sites in the 5′ NRE partially alleviated repression in the context of the 79-nt NRE but caused full derepression when assayed in a construct with the 3′ NRE deleted. All four contribute to the inhibitory effect, though the second splice site is most inhibitory. Sm proteins, U1A and U1 snRNA, but not U1 70K, could be affinity purified with the wild-type NRE but not with the NRE containing mutations in the 5′ splice sites, indicating that a U1 snRNP-like complex forms upon the element.

scholarly journals Splicing Control in Normal and Aberrant Erythropoiesis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. SCI-47-SCI-47
Author(s):  
Esther Obeng
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Iron Transport ◽  
Rna Binding ◽  
Intron Retention ◽  
Point Mutations ◽  
Cytoskeletal Proteins ◽  
Mrna Splicing ◽  
Splice Sites ◽  
Erythroid Maturation

Abstract Alternative splicing is employed by all eukaryotic cells to increase proteome diversity and to regulate gene expression. RNA sequencing analysis of purified populations of erythroblasts at different stages of maturation has led to the identification of a dynamic alternative splicing program that directly modulates the protein isoform expression of cytoskeletal proteins and genes involved in RNA processing, heme biosynthesis, and iron transport. Regulated interactions of multiple RNA-binding proteins and cis-regulatory sequences located within exons or their flanking introns promote or inhibit functional spliceosome assembly at splice junctions, leading to altered exon inclusion or intron retention. Exon skipping regulates tissue and stage specific isoform expression of red cell membrane cytoskeletal proteins including EPB41, ankyrin, and band 3. Intron retention can lead to a frame shift during translation and introduction of a premature termination codon (PTC), that marks the transcript for degradation via the nonsense mediated decay pathway (NMD) upon export from the nucleus into the cytoplasm. Intron retention leading to posttranscriptional regulation of gene expression during terminal erythroid maturation has been identified in genes involved in RNA processing and iron transport including SF3B1, SNRNP70, SLC25A37 and SLC25A28. Mutations that alter mRNA splice sites or introduce PTCs lead to a variety of congenital anemias including beta thalassemia, hereditary pyropoikilocytosis, hereditary elliptocytosis, and hereditary spherocytosis. Aberrant mRNA splicing has subsequently been shown to lead to acquired anemias in subsets of patients with myelodysplastic syndromes (MDS). Somatic missense mutations in components of the spliceosome are the most common category of mutations in MDS. These point mutations lead to changes in the RNA binding specificity of the involved proteins and aberrant splicing of a subset of transcripts. Mutant SF3B1, the most commonly mutated splicing factor in MDS, has been shown to cause aberrant pre-mRNA splicing and an increase in transcripts predicted to undergo NMD due to use of upstream, cryptic 3' splice sites. Our group and others evaluating the strong genotype-phenotype association between SF3B1 point mutations and subtypes of MDS with ring sideroblasts have shown that the expression of the mitochondrial iron transporter, ABCB7, is decreased in samples from SF3B1-mutant MDS patients due to cryptic 3' splice site selection and introduction of a PTC between exons 8 and 9. The identification and functional validation of additional aberrantly spliced mutant-SF3B1 target genes is ongoing, with the goal of understanding how point mutations in a core component of the mRNA splicing machinery can lead to such specific effects on erythroid maturation. Disclosures No relevant conflicts of interest to declare.

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 The genomes of polyextremophilic cyanidiales contain 1% horizontally transferred genes with diverse adaptive functions

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alessandro W Rossoni ◽  
Dana C Price ◽  
Mark Seger ◽  
Dagmar Lyska ◽  
Peter Lammers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gc Content ◽  
Cumulative Effects ◽  
Foreign Gene ◽  
Splice Sites ◽  
Pan Genome ◽  
Gene Acquisition ◽  
Close Phylogenetic Relationship ◽  
Selection For

The role and extent of horizontal gene transfer (HGT) in eukaryotes are hotly disputed topics that impact our understanding of the origin of metabolic processes and the role of organelles in cellular evolution. We addressed this issue by analyzing 10 novel Cyanidiales genomes and determined that 1% of their gene inventory is HGT-derived. Numerous HGT candidates share a close phylogenetic relationship with prokaryotes that live in similar habitats as the Cyanidiales and encode functions related to polyextremophily. HGT candidates differ from native genes in GC-content, number of splice sites, and gene expression. HGT candidates are more prone to loss, which may explain the absence of a eukaryotic pan-genome. Therefore, the lack of a pan-genome and cumulative effects fail to provide substantive arguments against our hypothesis of recurring HGT followed by differential loss in eukaryotes. The maintenance of 1% HGTs, even under selection for genome reduction, underlines the importance of non-endosymbiosis related foreign gene acquisition.

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 cytosine-rich splice regulatory determinant enforces functional processing of the human α-globin gene transcript

Blood ◽  
2019 ◽  
Vol 133 (21) ◽  
pp. 2338-2347 ◽  
Author(s):  
Xinjun Ji ◽  
Jesse Humenik ◽  
Stephen A. Liebhaber
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Globin Gene ◽  
Donor Site ◽  
Primate Species ◽  
Gene Transcript ◽  
Splice Sites ◽  
Splice Donor ◽  
Differentiated Cells ◽  
Globin Gene Expression

Abstract The establishment of efficient and stable splicing patterns in terminally differentiated cells is critical to maintenance of specific functions throughout the lifespan of an organism. The human α-globin (hα-globin) gene contains 3 exons separated by 2 short introns. Naturally occurring α-thalassemia mutations that trigger aberrant splicing have revealed the presence of cryptic splice sites within the hα-globin gene transcript. How cognate (functional) splice sites are selectively used in lieu of these cryptic sites has remained unexplored. Here we demonstrate that the preferential selection of a cognate splice donor essential to functional splicing of the hα-globin transcript is dependent on the actions of an intronic cytosine (C)-rich splice regulatory determinant and its interacting polyC-binding proteins. Inactivation of this determinant by mutation of the C-rich element or by depletion of polyC-binding proteins triggers a dramatic shift in splice donor activity to an upstream, out-of-frame, cryptic donor. The essential role of the C-rich element in hα-globin gene expression is supported by its coevolution with the cryptic donor site in primate species. These data lead us to conclude that an intronic C-rich determinant enforces functional splicing of the hα-globin transcript, thus acting as an obligate determinant of hα-globin gene expression.

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.

scholarly journals The Exon Junction Complex and intron removal prevents resplicing of mRNA

2020 ◽  
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 ◽  
Exon Junctions ◽  
Intron Removal ◽  
Cryptic Splice Sites

AbstractAccurate splice site selection is critical for fruitful gene expression. Here, we demonstrate the Drosophila EJC suppresses hundreds of functional cryptic splice sites (SS), even though majority of these bear weak splicing motifs and appear incompetent. Mechanistically, the EJC directly conceals splicing elements through position-specific recruitment, preventing SS definition. We note that intron removal using strong, canonical SS yields AG|GU signatures at exon-exon junctions. Unexpectedly, we discover that scores of these minimal exon junction sequences are in fact EJC-suppressed 5’ and 3’ recursive SS, and that loss of EJC regulation from such transcripts triggers faulty mRNA resplicing. An important corollary is that intronless cDNA expression constructs from aforementioned targets yield high levels of unanticipated, truncated transcripts generated by resplicing. Consequently, we conclude the EJC has ancestral 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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