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Putative alternative polyadenylation (APA) events in the early interaction of Salmonella enterica Typhimurium and human host cells.

Afonso-Grunz F - Genom Data (2015)

Bottom Line: Abstract available from the publisher.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular BioSciences, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.

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Alternative polyadenylation (APA) is a common regulatory mechanism of gene expression that generates messenger RNAs (mRNAs) with distinct untranslated regions (UTRs) as well as coding sequences from one and the same gene... The resulting transcript isoforms may not only exhibit an altered coding potential, but also harbor a distinct set of cis-regulatory elements for microRNAs (miRNAs) and other non-coding RNAs (ncRNAs) as well as RNA-binding proteins (RBPs) that affects processing, localization, stability, and translation of the mRNA... Poly(A)-position profiling by sequencing (3P-Seq ) represents another technique for global detection of PA site usage besides MACE (reviewed in ), and a recent publication features a 3P-Seq dataset of cultured HeLa cells that were grown under similar conditions as in the present study... We previously compared the high-confidence PA sites in the 3P-Seq dataset of mouse liver cells from Nam and colleagues with those obtained by MACE, and concluded that 3P-Seq and MACE provide similar results... The generated list of clusters (Supplementary Table S1) was screened for gene-specific PA sites present both in uninfected and early interacting cells... Further filtering resulted in 142 significantly differentially used PA sites (Bonferroni-adjusted p-value < 0.05) within 130 different genes... Another gene that gives rise to mRNAs with distinct 3′ UTRs encodes Peroxiredoxin 1 (PRDX1)... The predicted motifs mostly comprise binding sites of heterogeneous nuclear ribonucleoproteins (hnRNPs), followed by members of the serine/arginine (SR)-rich family of pre-mRNA splicing factors (SRSFs) along with other proteins that influence alternative splicing, transport and translation efficiency of PRDX1 (Supplementary Table S2)... The five highest ranking motifs are listed in Table 2 together with their associated RBPs... While this represents a common mechanism in prokaryotes, cytosolic polyadenylation was only relatively recently shown to contribute to RNA degradation in humans... The presence of degradation intermediates would indicate reduced levels of the labile iron pool caused by the increased iron consumption that arises from additional uptake of iron into intracellular bacteria... The highest ranking RBP motif in the region between the two major PA sites of PRDX1 recruits MATR3, an inner nuclear matrix protein that stabilizes mRNAs upon binding and that additionally binds to small ncRNAs involved in splicing... Besides their role in alternative splicing, several of the identified RBPs are involved in transport and translation of mRNAs... The comparison of the identified polyadenylation landscape in early interacting cells with the published dataset of non-interacting cells determined by 3P-Seq indicates several significantly differentially used PA sites, and some of these suggest that APA might contribute to the complex regulatory network that governs the immune response of epithelial cells... APA of PRDX1 results in transcription of mRNA isoforms with distinct sets of miRNA binding sites, while PA site usage in VAPA is likely to influence alternative splicing.

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APA in the 3′ UTR of VAPA from uninfected and early interacting host cells. Depicted is the region that encodes the 3′ UTR of VAPA on human chromosome 18. The number of poly(A) tail positive reads is shown for each cluster along with the 3′ UTR miRNA binding sites of VAPA[31]. PA site usage differs in between three sites that give rise to mRNAs with several lost or gained miRNA binding sites. Please consult Fig. 2 for further details.
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f0015: APA in the 3′ UTR of VAPA from uninfected and early interacting host cells. Depicted is the region that encodes the 3′ UTR of VAPA on human chromosome 18. The number of poly(A) tail positive reads is shown for each cluster along with the 3′ UTR miRNA binding sites of VAPA[31]. PA site usage differs in between three sites that give rise to mRNAs with several lost or gained miRNA binding sites. Please consult Fig. 2 for further details.

Mentions: VAMP (vesicle-associated membrane protein)-associated protein A (VAPA) represents an endoplasmic reticulum (ER)-bound type IV membrane protein that regulates intracellular vesicle trafficking. The 3′ UTR of VAPA comprises numerous miRNA binding sites and exhibits three PA sites in non-interacting HeLa cells, while PA site usage in early interacting cells is restricted to a single site (Fig. 3). The 3′ UTR isoform that is also present in early interacting cells only constitutes 16% of all VAPA isoforms in uninfected cells. The most abundant isoform in non-interacting cells (almost 50% of all isoforms) is considerably shorter compared to the isoform that is also present in early interacting cells (~ 320 nucleotides difference on average), and lacks the binding sites for miR-543, miR-194, miR-335/335-5p, miR-875-5p, miR-505/505-3p as well as miR-132/212/212-3p. In contrast, the third and most distal PA site that is present in non-interacting cells gives rise to a 3′ UTR isoform that additionally harbors binding sites for miR-93/93a/105/106a/291a-3p/294/295/302abcde/372/373/428/519a/520be/520acd-3p/1378/1420ac, miR-23abc/23b-3p, miR-145, miR-200bc/429/548a, miR-203, and miR-340-5p.


Putative alternative polyadenylation (APA) events in the early interaction of Salmonella enterica Typhimurium and human host cells.

Afonso-Grunz F - Genom Data (2015)

APA in the 3′ UTR of VAPA from uninfected and early interacting host cells. Depicted is the region that encodes the 3′ UTR of VAPA on human chromosome 18. The number of poly(A) tail positive reads is shown for each cluster along with the 3′ UTR miRNA binding sites of VAPA[31]. PA site usage differs in between three sites that give rise to mRNAs with several lost or gained miRNA binding sites. Please consult Fig. 2 for further details.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664775&req=5

f0015: APA in the 3′ UTR of VAPA from uninfected and early interacting host cells. Depicted is the region that encodes the 3′ UTR of VAPA on human chromosome 18. The number of poly(A) tail positive reads is shown for each cluster along with the 3′ UTR miRNA binding sites of VAPA[31]. PA site usage differs in between three sites that give rise to mRNAs with several lost or gained miRNA binding sites. Please consult Fig. 2 for further details.
Mentions: VAMP (vesicle-associated membrane protein)-associated protein A (VAPA) represents an endoplasmic reticulum (ER)-bound type IV membrane protein that regulates intracellular vesicle trafficking. The 3′ UTR of VAPA comprises numerous miRNA binding sites and exhibits three PA sites in non-interacting HeLa cells, while PA site usage in early interacting cells is restricted to a single site (Fig. 3). The 3′ UTR isoform that is also present in early interacting cells only constitutes 16% of all VAPA isoforms in uninfected cells. The most abundant isoform in non-interacting cells (almost 50% of all isoforms) is considerably shorter compared to the isoform that is also present in early interacting cells (~ 320 nucleotides difference on average), and lacks the binding sites for miR-543, miR-194, miR-335/335-5p, miR-875-5p, miR-505/505-3p as well as miR-132/212/212-3p. In contrast, the third and most distal PA site that is present in non-interacting cells gives rise to a 3′ UTR isoform that additionally harbors binding sites for miR-93/93a/105/106a/291a-3p/294/295/302abcde/372/373/428/519a/520be/520acd-3p/1378/1420ac, miR-23abc/23b-3p, miR-145, miR-200bc/429/548a, miR-203, and miR-340-5p.

Bottom Line: Abstract available from the publisher.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular BioSciences, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Alternative polyadenylation (APA) is a common regulatory mechanism of gene expression that generates messenger RNAs (mRNAs) with distinct untranslated regions (UTRs) as well as coding sequences from one and the same gene... The resulting transcript isoforms may not only exhibit an altered coding potential, but also harbor a distinct set of cis-regulatory elements for microRNAs (miRNAs) and other non-coding RNAs (ncRNAs) as well as RNA-binding proteins (RBPs) that affects processing, localization, stability, and translation of the mRNA... Poly(A)-position profiling by sequencing (3P-Seq ) represents another technique for global detection of PA site usage besides MACE (reviewed in ), and a recent publication features a 3P-Seq dataset of cultured HeLa cells that were grown under similar conditions as in the present study... We previously compared the high-confidence PA sites in the 3P-Seq dataset of mouse liver cells from Nam and colleagues with those obtained by MACE, and concluded that 3P-Seq and MACE provide similar results... The generated list of clusters (Supplementary Table S1) was screened for gene-specific PA sites present both in uninfected and early interacting cells... Further filtering resulted in 142 significantly differentially used PA sites (Bonferroni-adjusted p-value < 0.05) within 130 different genes... Another gene that gives rise to mRNAs with distinct 3′ UTRs encodes Peroxiredoxin 1 (PRDX1)... The predicted motifs mostly comprise binding sites of heterogeneous nuclear ribonucleoproteins (hnRNPs), followed by members of the serine/arginine (SR)-rich family of pre-mRNA splicing factors (SRSFs) along with other proteins that influence alternative splicing, transport and translation efficiency of PRDX1 (Supplementary Table S2)... The five highest ranking motifs are listed in Table 2 together with their associated RBPs... While this represents a common mechanism in prokaryotes, cytosolic polyadenylation was only relatively recently shown to contribute to RNA degradation in humans... The presence of degradation intermediates would indicate reduced levels of the labile iron pool caused by the increased iron consumption that arises from additional uptake of iron into intracellular bacteria... The highest ranking RBP motif in the region between the two major PA sites of PRDX1 recruits MATR3, an inner nuclear matrix protein that stabilizes mRNAs upon binding and that additionally binds to small ncRNAs involved in splicing... Besides their role in alternative splicing, several of the identified RBPs are involved in transport and translation of mRNAs... The comparison of the identified polyadenylation landscape in early interacting cells with the published dataset of non-interacting cells determined by 3P-Seq indicates several significantly differentially used PA sites, and some of these suggest that APA might contribute to the complex regulatory network that governs the immune response of epithelial cells... APA of PRDX1 results in transcription of mRNA isoforms with distinct sets of miRNA binding sites, while PA site usage in VAPA is likely to influence alternative splicing.

No MeSH data available.