scholarly journals Profiling novel alternative splicing within multiple tissues puts insight into the porcine genome annotation

2019 ◽  
Author(s):  
Wen Feng ◽  
Pengju Zhao ◽  
Xianrui Zheng ◽  
Jian-Feng Liu
Keyword(s):  
Alternative Splicing ◽  
Rna Sequencing ◽  
Genome Annotation ◽  
Intron Retention ◽  
Donor Site ◽  
Exon Skipping ◽  
Acceptor Site ◽  
Novel Proteins ◽  
Genome Wide ◽  
Alternative Donor

Abstract Background Alternative splicing (AS) is a process that mRNA precursor splices intron to form the mature mRNA. AS plays important roles in contributing to transcriptome and proteome divert. However, to date there is no research about pig AS in genome-wide level by RNA sequencing. Results To characterize the AS in pigs, herein we detected genome-wide transcripts and events by RNA sequencing technology (RNA-seq) 34 different tissues in Duroc pigs. In total, we identified 138, 403 AS events and 29, 270 expressed genes. We found alternative donor site was the most common AS form, which is accounted for 44% of the total AS events. The percentage of the other 3 AS forms (Exon skipping, Alternative acceptor site and Intron retention) are all around 19%. The results showed that the most common AS events (alternative donor site) can produce different transcripts or different proteins which affect the biological process. Among these AS events, 109, 483 were novel AS events, and the number of alternative donor splice site has increased the most (Accounting for 44% of the novel AS events). Conclusions The expression of gene with tissue specific AS events showed that the functions of these genes were consistent with the tissue function. AS increased proteome diversity and resulted in novel proteins that gained and lost important functional domains. In summary, these findings extend genome annotation and highlight roles that AS acts in tissue identity in pig.

Profiling novel alternative splicing within multiple tissues puts insight into the porcine genome annotation

2019 ◽  
Author(s):  
Jian-Feng Liu ◽  
Wen Feng ◽  
Pengju Zhao ◽  
Xianrui Zheng
Keyword(s):  
Alternative Splicing ◽  
Rna Sequencing ◽  
Genome Annotation ◽  
Donor Site ◽  
The Novel ◽  
Rna Seq ◽  
Novel Proteins ◽  
Genome Wide ◽  
Alternative Donor ◽  
Mrna Precursor

Abstract Background Alternative splicing (AS) is a process that mRNA precursor splices intron to form the mature mRNA. AS plays important roles in contributing to transcriptome and proteome divert. However, to date there is no research about pig AS in genome-wide level by RNA sequencing. Results To characterize the AS in pigs, herein we detected genome-wide transcripts and events by RNA sequencing technology (RNA-seq) 34 different tissues in Duroc pigs. In total, we identified 138, 403 AS events and 29, 270 expressed genes. We found alternative donor site was the most common AS form, which is accounted for 44% of the total AS events. The percentage of the other 3 AS forms are all around 19%. The results showed that the most common AS events (alternative donor site) can produce different transcripts or different proteins which affect the biological process. Among these AS events, 109, 483 were novel AS events, and the number of alternative donor splice site has increased the most (Accounting for 44% of the novel AS events).Conclusions The expression of gene with tissue specific AS events showed that the functions of these genes were consistent with the tissue function. AS increased proteome diversity and resulted in novel proteins that gained and lost important functional domains. In summary, these findings extend genome annotation and highlight roles that AS acts in tissue identity in pig.Key words: Alternative splicing; transcript; protein; SNP

scholarly journals Profiling Novel Alternative Splicing within Multiple Tissues Provides Useful Insights into Porcine Genome Annotation

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1405
Author(s):  
Wen Feng ◽  
Pengju Zhao ◽  
Xianrui Zheng ◽  
Zhengzheng Hu ◽  
Jianfeng Liu
Keyword(s):  
Alternative Splicing ◽  
Genome Annotation ◽  
Intron Retention ◽  
Single Gene ◽  
Donor Site ◽  
Exon Skipping ◽  
Acceptor Site ◽  
Porcine Genome ◽  
Expression Of Genes ◽  
Alternative Donor

Alternative splicing (AS) is a process during gene expression that results in a single gene coding for different protein variants. AS contributes to transcriptome and proteome diversity. In order to characterize AS in pigs, genome-wide transcripts and AS events were detected using RNA sequencing of 34 different tissues in Duroc pigs. In total, 138,403 AS events and 29,270 expressed genes were identified. An alternative donor site was the most common AS form and accounted for 44% of the total AS events. The percentage of the other three AS forms (exon skipping, alternative acceptor site, and intron retention) was approximately 19%. The results showed that the most common AS events involving alternative donor sites could produce different transcripts or proteins that affect the biological processes. The expression of genes with tissue-specific AS events showed that gene functions were consistent with tissue functions. AS increased proteome diversity and resulted in novel proteins that gained or lost important functional domains. In summary, these findings extend porcine genome annotation and highlight roles that AS could play in determining tissue identity.

scholarly journals Alternative Splicing During the Chlamydomonasreinhardtii Cell Cycle

2020 ◽  
Vol 10 (10) ◽  
pp. 3797-3810
Author(s):  
Manishi Pandey ◽  
Gary D. Stormo ◽  
Susan K. Dutcher
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Alternative Splicing ◽  
Chlamydomonas Reinhardtii ◽  
Intron Retention ◽  
Exon Skipping ◽  
Dark Phase ◽  
Periodic Patterns ◽  
Genome Wide ◽  
Splicing Pattern

Genome-wide analysis of transcriptome data in Chlamydomonas reinhardtii shows periodic patterns in gene expression levels when cultures are grown under alternating light and dark cycles so that G1 of the cell cycle occurs in the light phase and S/M/G0 occurs during the dark phase. However, alternative splicing, a process that enables a greater protein diversity from a limited set of genes, remains largely unexplored by previous transcriptome based studies in C. reinhardtii. In this study, we used existing longitudinal RNA-seq data obtained during the light-dark cycle to investigate the changes in the alternative splicing pattern and found that 3277 genes (19.75% of 17,746 genes) undergo alternative splicing. These splicing events include Alternative 5′ (Alt 5′), Alternative 3′ (Alt 3′) and Exon skipping (ES) events that are referred as alternative site selection (ASS) events and Intron retention (IR) events. By clustering analysis, we identified a subset of events (26 ASS events and 10 IR events) that show periodic changes in the splicing pattern during the cell cycle. About two-thirds of these 36 genes either introduce a pre-termination codon (PTC) or introduce insertions or deletions into functional domains of the proteins, which implicate splicing in altering gene function. These findings suggest that alternative splicing is also regulated during the Chlamydomonas cell cycle, although not as extensively as changes in gene expression. The longitudinal changes in the alternative splicing pattern during the cell cycle captured by this study provides an important resource to investigate alternative splicing in genes of interest during the cell cycle in Chlamydomonas reinhardtii and other eukaryotes.

scholarly journals Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Guiomar Martín ◽  
Yamile Márquez ◽  
Federica Mantica ◽  
Paula Duque ◽  
Manuel Irimia
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Alternative Splicing ◽  
Stress Responses ◽  
Target Genes ◽  
Intron Retention ◽  
Single Gene ◽  
Exon Skipping ◽  
Environmental Response ◽  
Biotic Stresses

Abstract Background Alternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, especially environmental stress, unveiling substantial amounts of intron retention that modulate gene expression. However, a comprehensive study contrasting stress-response and tissue-specific AS patterns and directly comparing them with those of animal models is still missing. Results We generate a massive resource for Arabidopsis thaliana, PastDB, comprising AS and gene expression quantifications across tissues, development and environmental conditions, including abiotic and biotic stresses. Harmonized analysis of these datasets reveals that A. thaliana shows high levels of AS, similar to fruitflies, and that, compared to animals, disproportionately uses AS for stress responses. We identify core sets of genes regulated specifically by either AS or transcription upon stresses or among tissues, a regulatory specialization that is tightly mirrored by the genomic features of these genes. Unexpectedly, non-intron retention events, including exon skipping, are overrepresented across regulated AS sets in A. thaliana, being also largely involved in modulating gene expression through NMD and uORF inclusion. Conclusions Non-intron retention events have likely been functionally underrated in plants. AS constitutes a distinct regulatory layer controlling gene expression upon internal and external stimuli whose target genes and master regulators are hardwired at the genomic level to specifically undergo post-transcriptional regulation. Given the higher relevance of AS in the response to different stresses when compared to animals, this molecular hardwiring is likely required for a proper environmental response in A. thaliana.

scholarly journals Swan: a library for the analysis and visualization of long-read transcriptomes

2020 ◽  
Author(s):  
Fairlie Reese ◽  
Ali Mortazavi
Keyword(s):  
Rna Sequencing ◽  
Cell Lines ◽  
Intron Retention ◽  
Exon Skipping ◽  
Differentially Expressed ◽  
Transcript Isoforms ◽  
Sequencing Technologies ◽  
Oxford Nanopore ◽  
Long Read

Abstract Motivation Long-read RNA-sequencing technologies such as PacBio and Oxford Nanopore have discovered an explosion of new transcript isoforms that are difficult to visually analyze using currently available tools. We introduce the Swan Python library, which is designed to analyze and visualize transcript models. Results Swan finds 4909 differentially expressed transcripts between cell lines HepG2 and HFFc6, including 279 that are differentially expressed even though the parent gene is not. Additionally, Swan discovers 285 reproducible exon skipping and 47 intron retention events not recorded in the GENCODE v29 annotation. Availability and implementation The Swan library for Python 3 is available on PyPi at https://pypi.org/project/swan-vis/ and on GitHub at https://github.com/mortazavilab/swan_vis.

CML Developed in a Japanese Family Transmitting a Novel Point Mutation in the Thrombopoietin Gene(TPO).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4220-4220 ◽  
Author(s):  
Yasuo Oshima ◽  
Norio Komatsu ◽  
Keiya Ozawa ◽  
Akio Fujimura
Keyword(s):  
Point Mutation ◽  
Translational Regulation ◽  
Intron Retention ◽  
Leukemia Virus ◽  
Donor Site ◽  
Exon Skipping ◽  
Myeloproliferative Disorders ◽  
Complete Response ◽  
Japanese Family ◽  
Hematopoietic Stem

Abstract Introduction: Four families are reported to have hereditary thrombocythemia (HT) with a mutation in TPO. Their clinical manifestation is essentially thrombocytosis without leukemia. CML is one of myeloproliferative disorders, and shows leukocytosis and thrombocytosis associated with a proliferation of malignant clone originated from a hematopoietic stem cell (HSC). The incidence of CML is about 5 per 100,000 in Japan. Mutations of cytokine receptor including c-kit, flt-3 and G-CSF receptor are reported as a cause of AML. Especially flt-3 abnormalities are found in about 20% of AML. However, abnormality of c-mpl or TPO is not reported as a cause of leukemia. In this paper, we analyzed a CML case with novel point mutation in the TPO who still had thrombocytosis after cytogenetic complete response. Case: Japanese, 35 y.o., male, complained leukocytosis. He had a family history of thrombocytosis in 4 individuals over 3 generations. A physical examination revealed a moderate splenomegaly. Laboratory tests at the time of diagnosis were as follows; WBC 141,000/μl (blast 1.8%, promyelo 2.4%, myelo 20.0%, meta 8.2%, stab 24.2%, seg 22.2%, immature eosinophils 1.8%, eosinophil 3.6%, immature basophils 0.4%, basophils 10.4%, mono 1.0%, lymphocytes 4.0%, erythroblast 3%), PLT 641,000/μl and NAP score 53 (nl; 156–271). Bone marrow showed hypercellularity with the increased megakaryocytes(Meg), bcr-abl fusion mRNA positive, Ph1 chromosome positive. After 5 months treatment with STI571, most of clinical findings including karyotype and fusion mRNA turned to be normal, but thrombocyte(PLT) still showed more than 1,000,000/μl. At this time, serum TPO concentration was 8.14 f mole/ml (nl; 0.40 +/− 0.28 f mole/ml, mean +/− SD). Genetic analysis of TPO revealed novel point mutation at splicing donor site of 3′-end of the exon3. A point mutation at splicing donor site is reported to cause an exon-skipping and intron-retention, which induce a malfunction of a suppressive post-transcriptional and translational regulation, and consequent high-level expression of functional TPO protein. Discussion: TPO was cloned as a c-mpl ligand, which leads to the production of PLTs. Its receptor is a c-mpl proto-oncogene product, which is expressed not only in Meg, but also in HSC. Thus, TPO can stimulate HSC. The c-mpl transgenic mice are reported to have the increased Meg, its committed progenitor and PLT. Knockout mice of TPO presented not only the decreased Meg, but also multi-lineage committed progenitors. Thus, a modulation of c-mpl or its ligand function affects on both Meg and HSC. The c-mpl was cloned as a cellular homolog of a viral oncogene, v-mpl of myeloproliferative leukemia virus (MPL). The MPL causes myeloproliferative leukemia syndrome through v-mpl function in mice. Since v-mpl and c-mpl indicate high homology, it is possible that abnormal c-mpl function causes v-mpl like response. Through continuous stimulation of c-mpl signal, high TPO concentration may have induced a malignant transformation of HSC or supported a survival of an immature malignant clone in the present case. Improvement of thrombocytosis in CML is one of hematological responses to an anti-CML treatment such as STI571. In such a case who had good response other than thrombocytosis, an existence of HT might be considered. On the other hand, during following up HT family, occurrence of CML should be noted.

scholarly journals Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals

2020 ◽  
Author(s):  
Guiomar Martín ◽  
Yamile Márquez ◽  
Federica Mantica ◽  
Paula Duque ◽  
Manuel Irimia
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Stress Responses ◽  
Target Genes ◽  
Intron Retention ◽  
Single Gene ◽  
Exon Skipping ◽  
Environmental Response ◽  
Biotic Stresses ◽  
External Stimuli

AbstractBackgroundAlternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, especially environmental stress, unveiling substantial amounts of intron retention that modulate gene expression. However, a comprehensive study contrasting stress-response and tissue-specific AS patterns and directly comparing them with those of animal models is still missing.ResultsWe generated a massive resource for A. thaliana (PastDB; pastdb.crg.eu), comprising AS and gene expression quantifications across tissues, development and environmental conditions, including abiotic and biotic stresses. Harmonized analysis of these datasets revealed that A. thaliana shows high levels of AS (similar to fruitflies) and that, compared to animals, disproportionately uses AS for stress responses. We identified core sets of genes regulated specifically by either AS or transcription upon stresses or among tissues, a regulatory specialization that was tightly mirrored by the genomic features of these genes. Unexpectedly, non-intron retention events, including exon skipping, were overrepresented across regulated AS sets in A. thaliana, being also largely involved in modulating gene expression through NMD and uORF inclusion.ConclusionsNon-intron retention events have likely been functionally underrated in plants. AS constitutes a distinct regulatory layer controlling gene expression upon internal and external stimuli whose target genes and master regulators are hardwired at the genomic level to specifically undergo post-transcriptional regulation. Given the higher relevance of AS in the response to different stresses when compared to animals, this molecular hardwiring is likely required for a proper environmental response in A. thaliana.

scholarly journals The rapid evolution of alternative splicing in plants

2017 ◽  
Author(s):  
Zhihao Ling ◽  
Thomas Brockmöller ◽  
Ian T. Baldwin ◽  
Shuqing Xu
Keyword(s):  
Alternative Splicing ◽  
Related Species ◽  
Donor Site ◽  
Rapid Evolution ◽  
Acceptor Site ◽  
Mrna Levels ◽  
Evolutionary Patterns ◽  
Closely Related Species ◽  
Nonsense Mediated Decay ◽  
Splicing Regulators

AbstractAlternative pre-mRNA splicing (AS) is prevalent among all plants and is involved in many interactions with environmental stresses. However, the evolutionary patterns and underlying mechanisms of AS in plants remain unclear. By analyzing the transcriptomes of six plant species, we revealed that AS diverged rapidly among closely related species, largely due to the gains and losses of AS events among orthologous genes. Furthermore, AS that generates transcripts containing premature termination codons (PTC), although only representing a small fraction of the total AS, are more conserved than those that generate non-PTC containing transcripts, suggesting that AS coupled with nonsense-mediated decay (NMD) might play an important role in regulating mRNA levels post-transcriptionally. With a machine learning approach we analyzed the key determinants of AS to understand the mechanisms underlying its rapid divergence. Among the studied species, the presence/absence of alternative splicing site (SS) within the junction, the distance between the authentic SS and the nearest alternative SS, the size of exon-exon junctions were the major determinants for both alternative 5’ donor site and 3’acceptor site, suggesting a relatively conserved AS mechanism. Comparative analysis further demonstrated that variations of the identified AS determinants, mostly are located in introns, significantly contributed to the AS turnover among closely related species in both Solanaceae and Brassicaceae taxa. These new mechanistic insights into the evolution of AS in plants highlight the importance of post-transcriptional regulation in mediating plant-environment interactions.One sentence summaryChanges of intron located splicing regulators contributed to the rapid evolution of alternative splicing in plants.

scholarly journals Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018 ◽  
Author(s):  
Jin Li ◽  
Peng Yu
Keyword(s):  
Alternative Splicing ◽  
Computational Analysis ◽  
Potential Role ◽  
Exon Skipping ◽  
Chronic Inflammatory Disease ◽  
Splicing Factors ◽  
The Novel ◽  
Rna Seq ◽  
Genome Wide

AbstractPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For understanding the mechanism of psoriasis, though, alternative splicing analysis has received relatively little attention in the field. Here, we developed and applied several computational analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential alternative splicing analyses detected hundreds of differential alternative splicing changes. Our analysis of conservation revealed many exon-skipping events conserved between mice and humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. Three of the nine splicing factors were confirmed upon analyzing the human data. Our computational methods have generated predictions for the potential role of splicing in psoriasis. Future experiments on the novel candidates predicted by our computational analysis are expected to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for new therapeutic treatments.

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