The matrices and constraints of GT/AG splice sites of more than 1000 species/lineages

Nguyen, Hai Dang; Das, Urmi; Wang, Benjamin; Xie, Jiuyong

doi:10.1016/j.gene.2018.03.031

Cited by 10 publications

(32 citation statements)

References 80 publications

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“…The highest percentage of purine-rich 3'SS is 61% in the genome of fungus Edhazardia aedis, which is A/T-rich (38% each). Even in species that are highly constrained at certain positions for Ts within this region [1,21], such as the T -5 and T -8 in C. elegans and B. microti, respectively, and to a less extent the T -5 in B. bigemina, we still identified hundreds or thousands of purine-rich 3'SS ( Fig. 1).…”

Section: Distribution Of Repa G Tract-harbouring 3' Splice Sites Amonmentioning

confidence: 92%

“…The purine enrichment contrasts the Py-rich content of the average 3'SS matrices of the human or other genomes [1]. The highest percentage of purine-rich 3'SS is 61% in the genome of fungus Edhazardia aedis, which is A/T-rich (38% each).…”

Section: Distribution Of Repa G Tract-harbouring 3' Splice Sites Amonmentioning

confidence: 94%

“…We first calculated and identified 17,643,684 annotated purine-rich 3'SS (≥5 purines between the -10 and -3 positions) of 1175 eukaryotic species/lineages in the Ensembl releases R38/R91 ( Fig. 1, & S_Table_I for matrices of each species and sequences of each 3'SS), as in our previous reports [1,18].…”

Section: Distribution Of Repa G Tract-harbouring 3' Splice Sites Amonmentioning

confidence: 99%

“…Splice sites demarcate the boundaries between introns and exons for proper splicing of precursor RNA transcripts. Their sequences are constrained by a consensus but could be highly diverse among hundreds of species [1]. The diversity and flexibility may contribute to alternative pre-mRNA splicing as well as to the mutation effect in many diseases [2,3,4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The diversity and flexibility may contribute to alternative pre-mRNA splicing as well as to the mutation effect in many diseases [2,3,4,5]. The majority of 3' splice sites are comprised of the branch point, polypyrimidine tract and 3' AG dinucleotides with a consensus (Y) 20 NCAGgt in humans based on the whole genome data [1]. These motifs are recognized by splicing complexes/factors U2 snRNP, U2AF65 and U2AF35, respectively [6,7,8,9,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Widespread separation of the polypyrimidine tract from 3’ AG by G tracts in association with alternative exons in metazoa and plants

Nguyen

Xie

2018

Preprint

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SummaryAt the end of introns, the polypyrimidine tract (Py) is often close to the 3' AG in a consensus (Y) 20 NCAGgt in humans. Interestingly, we have found that they could also be separated by purine-rich elements including G tracts in thousands of human genes. These regulatory elements between the Py and 3'AG (REPA) mainly regulate alternative 3' splice sites (3'SS) and intron retention. Here we show their widespread distribution and special properties across kingdoms. The purine-rich 3'SS are found in up to about 60% of the introns among more than 1000 species/lineages by whole genome analysis, and up to 18% of these introns contain the REPA G tracts in about 2.4 millions of 3'SS in total. In particular, they are significantly enriched over their 3'SS and genome backgrounds in metazoa and plants, and highly associated with alternative splicing of genes in diverse functional clusters. They are also highly enriched (3-6 folds) in the canonical as well as aberrantly used 3' splice sites in cancer patients carrying mutations of the branch point factor SF3B1 or the 3'AG binding factor U2AF35. Moreover, the REPA G tract-harbouring 3'SS have significantly reduced occurrences of branch point (BP) motifs between the -24 and -4 positions, in particular absent from the -7 --5 positions in several model organisms examined.The more distant branch points are associated with increased occurrences of alternative splicing in human and zebrafish. The branch points, REPA G tracts and associated 3'SS motifs appear to have emerged differentially in a phylum-or species-specific way during evolution. Thus, there is widespread separation of the Py and 3'AG by REPA G tracts, likely evolved among different species or branches of life. This special 3'SS arrangement contributes to the generation of diverse transcript or protein isoforms in biological functions or diseases through alternative or aberrant splicing.

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Section: Distribution Of Repa G Tract-harbouring 3' Splice Sites Amonmentioning

confidence: 92%

Section: Distribution Of Repa G Tract-harbouring 3' Splice Sites Amonmentioning

confidence: 94%

Section: Distribution Of Repa G Tract-harbouring 3' Splice Sites Amonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Widespread separation of the polypyrimidine tract from 3’ AG by G tracts in association with alternative exons in metazoa and plants

Nguyen

Xie

2018

Preprint

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Comprehensive discovery of salt-responsive alternative splicing events based on Iso-Seq and RNA-seq in grapevine roots

Jin

Sun

et al. 2021

Environmental and Experimental Botany

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Genome-wide evolution of wobble base-pairing nucleotides of branchpoint motifs with increasing organismal complexity

2019

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How have the branchpoint motifs evolved in organisms of different complexity? Here we identified and examined the consensus motifs (R 1 C 2 T 3 R 4 A 5 Y 6 , R: A or G, Y: C or T) of 898 fungal genomes. In Ascomycota unicellular yeasts, the G 4 /A 4 ratio is mostly (98%) below 0.125 but increases sharply in multicellular species by about 40 times on average, and in the more complex Basidiomycota, it increases further by about 7 times. The global G 4 increase is consistent with A 4 to G 4 transitions in evolution. Of the G 4 /A 4 -interacting amino acids of the branchpoint binding protein MSL5 (SF1) and the HSH155 (SF3B1), as well as the 5ʹ splice sites (SS) and U2 snRNA genes, the 5ʹ SS G 3 /A 3 co-vary with the G 4 to some extent. However, corresponding increase of the G 4 -complementary GCAGTA-U2 gene is rare, suggesting wobble-base pairing between the G 4 -containing branchpoint motif and GTAGTA-U2 in most of these species. Interestingly, the G 4 /A 4 ratio correlates well with the abundance of alternative splicing in the two phyla, and G 4 enriched significantly at the alternative 3' SS of genes in RNA metabolism, kinases and membrane proteins. Similar wobble nucleotides also enriched at the 3' SS of multicellular fungi with only thousands of protein-coding genes. Thus, branchpoint motifs have evolved U2-complementarity in unicellular Ascomycota yeasts, but have gradually gained more wobble base-pairing nucleotides in fungi of higher complexity, likely to destabilize branchpoint motif-U2 interaction and/or branchpoint A protrusion for alternative splicing. This implies an important role of relaxing the branchpoint signals in the multicellularity and further complexity of fungi.

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The matrices and constraints of GT/AG splice sites of more than 1000 species/lineages

Cited by 10 publications

References 80 publications

Widespread separation of the polypyrimidine tract from 3’ AG by G tracts in association with alternative exons in metazoa and plants

Widespread separation of the polypyrimidine tract from 3’ AG by G tracts in association with alternative exons in metazoa and plants

Comprehensive discovery of salt-responsive alternative splicing events based on Iso-Seq and RNA-seq in grapevine roots

Genome-wide evolution of wobble base-pairing nucleotides of branchpoint motifs with increasing organismal complexity

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