Two Alternative Splicing Variants of AtERF73/HRE1, HRE1α and HRE1β, Have Differential Transactivation Activities in Arabidopsis

AtERF73/HRE1 is an AP2/ERF transcription factor in Arabidopsis and has two distinct alternative splicing variants, HRE1α and HRE1β. In this study, we examined the differences between the molecular functions of HRE1α and HRE1β. We found that HRE1α and HRE1β are both involved in hypoxia response and root development and have transactivation activity. Two conserved motifs in the C-terminal region of HRE1α and HRE1β, EELL and LWSY-like, contributed to their transactivation activity, specifically the four E residues in the EELL motif and the MGLWS amino acid sequence at the end of the LWSY-like motif. The N-terminal region of HRE1β also showed transactivation activity, mediated by the VDDG motif, whereas that of HRE1α did not. The transactivation activity of HRE1β was stronger than that of HRE1α in Arabidopsis protoplasts. Both transcription factors transactivated downstream genes via the GCC box. RNA-sequencing analysis further supported that both HRE1α and HRE1β might regulate gene expression associated with the hypoxia stress response, although they may transactivate different subsets of genes in downstream pathways. Our results, together with previous studies, suggested that HRE1α and HRE1β differentially transactivate downstream genes in hypoxia response and root development in Arabidopsis.

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Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells

Genes ◽

10.3390/genes12050737 ◽

2021 ◽

Vol 12 (5) ◽

pp. 737

Author(s):

Ji-Eun Jeong ◽

Binna Seol ◽

Han-Seop Kim ◽

Jae-Yun Kim ◽

Yee-Sook Cho

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Alternative Splicing ◽

Functional Enrichment ◽

Actin Binding ◽

Pcr Analysis ◽

Valuable Insight ◽

Sequencing Analysis ◽

Induced Pluripotent ◽

Insight Into

Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 3′ (15.2%) and 5′ (12.8%) splice sites, and mutually exclusive exons (9.1%). Functional enrichment analysis showed that the differentially spliced genes (|FC| > 2 and BF > 20) were mainly enriched in functions associated with focal adhesion, extracellular exosomes, extracellular matrix organization, cell adhesion, and actin binding. Splice isoforms of selected genes including TRPT1, CNN2, and AP1G2, identified in sashimi plots, were further validated by RT-PCR analysis. This study provides valuable insight into the biology of iMSCs and the translation of mechanistic understanding of iMSCs into therapeutic applications.

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Alternative splicing variants of carbonic anhydrase IX in human non-small cell lung cancer

Lung Cancer ◽

10.1016/j.lungcan.2008.10.001 ◽

2009 ◽

Vol 64 (3) ◽

pp. 271-276 ◽

Cited By ~ 21

Author(s):

Francesca Malentacchi ◽

Lisa Simi ◽

Caterina Nannelli ◽

Matteo Andreani ◽

Alberto Janni ◽

...

Keyword(s):

Lung Cancer ◽

Alternative Splicing ◽

Carbonic Anhydrase ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Carbonic Anhydrase Ix ◽

Small Cell Lung ◽

Splicing Variants

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Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay

Molecular and Cellular Biology ◽

10.1128/mcb.00361-08 ◽

2008 ◽

Vol 28 (13) ◽

pp. 4320-4330 ◽

Cited By ~ 126

Author(s):

Arneet L. Saltzman ◽

Yoon Ki Kim ◽

Qun Pan ◽

Matthew M. Fagnani ◽

Lynne E. Maquat ◽

...

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Mrna Decay ◽

Splice Variants ◽

Cellular Functions ◽

Regulate Gene Expression ◽

Premature Termination Codons ◽

Microarray Profiling ◽

Nonsense Mediated Mrna Decay ◽

Regulate Gene

ABSTRACT Alternative splicing (AS) can regulate gene expression by introducing premature termination codons (PTCs) into spliced mRNA that subsequently elicit transcript degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the range of cellular functions controlled by this process and the factors required are poorly understood. By quantitative AS microarray profiling, we find that there are significant overlaps among the sets of PTC-introducing AS events affected by individual knockdown of the three core human NMD factors, Up-Frameshift 1 (UPF1), UPF2, and UPF3X/B. However, the levels of some PTC-containing splice variants are less or not detectably affected by the knockdown of UPF2 and/or UPF3X, compared with the knockdown of UPF1. The intron sequences flanking the affected alternative exons are often highly conserved, suggesting important regulatory roles for these AS events. The corresponding genes represent diverse cellular functions, and surprisingly, many encode core spliceosomal proteins and assembly factors. We further show that conserved, PTC-introducing AS events are enriched in genes that encode core spliceosomal proteins. Where tested, altering the expression levels of these core spliceosomal components affects the regulation of PTC-containing splice variants from the corresponding genes. Together, our results show that AS-coupled NMD can have different UPF factor requirements and is likely to regulate many general components of the spliceosome. The results further implicate general spliceosomal components in AS regulation.

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Five alternative splicing variants of the TYR gene and their different roles in melanogenesis in the Muchuan black-boned chicken

British Poultry Science ◽

10.1080/00071668.2018.1533633 ◽

2018 ◽

Vol 60 (1) ◽

pp. 8-14 ◽

Cited By ~ 3

Author(s):

S. Yu ◽

G. Wang ◽

J. Liao ◽

M. Tang

Keyword(s):

Alternative Splicing ◽

Splicing Variants ◽

Tyr Gene

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Insights into Telomerase/hTERT Alternative Splicing Regulation Using Bioinformatics and Network Analysis in Cancer

Cancers ◽

10.3390/cancers11050666 ◽

2019 ◽

Vol 11 (5) ◽

pp. 666 ◽

Cited By ~ 11

Author(s):

Andrew T. Ludlow ◽

Aaron L. Slusher ◽

Mohammed E. Sayed

Keyword(s):

Alternative Splicing ◽

Cancer Cells ◽

Rna Processing ◽

Splicing Regulation ◽

Cancer Cell Growth ◽

Growth And Survival ◽

Htert Gene ◽

Splicing Variants ◽

Cis And Trans ◽

Telomerase Regulation

The reactivation of telomerase in cancer cells remains incompletely understood. The catalytic component of telomerase, hTERT, is thought to be the limiting component in cancer cells for the formation of active enzymes. hTERT gene expression is regulated at several levels including chromatin, DNA methylation, transcription factors, and RNA processing events. Of these regulatory events, RNA processing has received little attention until recently. RNA processing and alternative splicing regulation have been explored to understand how hTERT is regulated in cancer cells. The cis- and trans-acting factors that regulate the alternative splicing choice of hTERT in the reverse transcriptase domain have been investigated. Further, it was discovered that the splicing factors that promote the production of full-length hTERT were also involved in cancer cell growth and survival. The goals are to review telomerase regulation via alternative splicing and the function of hTERT splicing variants and to point out how bioinformatics approaches are leading the way in elucidating the networks that regulate hTERT splicing choice and ultimately cancer growth.

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