scholarly journals Alternative Splicing of Pre-mRNA in the Control of Immune Activity

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 574
Author(s):  
Zhongjing Su ◽  
Dongyang Huang
Keyword(s):  
Alternative Splicing ◽  
Immune Cell ◽  
Splice Variants ◽  
Transcriptional Level ◽  
Aberrant Splicing ◽  
Immune Activity ◽  
Complex Process ◽  
Clinical Disorders ◽  
Human Immune Response ◽  
Alternative Splice Variants

The human immune response is a complex process that responds to numerous exogenous antigens in preventing infection by microorganisms, as well as to endogenous components in the surveillance of tumors and autoimmune diseases, and a great number of molecules are necessary to carry the functional complexity of immune activity. Alternative splicing of pre-mRNA plays an important role in immune cell development and regulation of immune activity through yielding diverse transcriptional isoforms to supplement the function of limited genes associated with the immune reaction. In addition, multiple factors have been identified as being involved in the control of alternative splicing at the cis, trans, or co-transcriptional level, and the aberrant splicing of RNA leads to the abnormal modulation of immune activity in infections, immune diseases, and tumors. In this review, we summarize the recent discoveries on the generation of immune-associated alternative splice variants, clinical disorders, and possible regulatory mechanisms. We also discuss the immune responses to the neoantigens produced by alternative splicing, and finally, we issue some alternative splicing and immunity correlated questions based on our knowledge.

Characterization of three alternative splice variants associated with the Arabidopsis rhomboid protein gene At1g74130

Botany ◽  
2013 ◽  
Vol 91 (12) ◽  
pp. 840-849 ◽  
Author(s):  
Joshua Powles ◽  
Katharine Sedivy-Haley ◽  
Eric Chapman ◽  
Kenton Ko
Keyword(s):  
Alternative Splicing ◽  
Alternative Splice ◽  
Splice Variant ◽  
Serine Proteases ◽  
Transmembrane Domain ◽  
Splice Variants ◽  
Genes Encoding ◽  
Different Characteristics ◽  
Alternative Splice Variants

Rhomboid serine proteases are grouped into three main types — secretases, presenilin-like associated rhomboid-like (PARL) proteases, and “inactive” rhomboid proteins. Although the three rhomboid groups are distinct, the different types are likely to operate within the same cell or compartment, such as observed in the plastids of Arabidopsis. There are four distinct plastid rhomboid genes at play in Arabidopsis plastids, two for active types (At1g25290 and At5g25752) and two for inactive forms (At1g74130 and At1g74140). The number of working plastid rhomboids is further increased by alternative splicing, as reported for At1g25290. To understand how the plastid rhomboid system works, it is necessary to identify all rhomboid forms in play. To this end, this study was designed to examine the alternative splicing activities of At1g74130, one of the two genes encoding proteolytically “inactive” plastid rhomboids. The exon mapping and DNA sequencing results obtained here indicate the presence of three prominent alternative splice variants in the At1g74130 transcript population. The dominant splice variant, L, encodes the full-length protein. The other two splice variants, M and S, produce proteins lacking sections from the carboxyl transmembrane domain region. The splice variants M and S appear to be at levels with functional potential and appear to adjust relative to each other during development and in response to changes in the level of Tic40, a component of the plastid translocon. The splice variant proteins themselves exhibit different characteristics with respect to rhomboid protein–substrate interactions. These differences were observed in bacterial co-expression pull-down assays and in yeast mitochondrial studies. When considered together, the data suggest that the alternative splicing of At1g74130 bears functional significance in Arabidopsis and is likely to be part of a mechanism for diversifying plastid rhomboid function.

scholarly journals Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

2016 ◽  
Vol 7 (2) ◽  
pp. 117-132 ◽  
Author(s):  
Katrina Viloria ◽  
Natasha J. Hill
Keyword(s):  
Alternative Splicing ◽  
Clinical Significance ◽  
Splice Variants ◽  
Single Gene ◽  
Matricellular Proteins ◽  
Surface Receptors ◽  
Cellular Processes ◽  
Clinical Disorders ◽  
The Matrix ◽  
Per Gene

AbstractMatricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets.

Characterization of two alternative splice variants associated with the Arabidopsis rhomboid protein gene At1g25290

Botany ◽  
2012 ◽  
Vol 90 (12) ◽  
pp. 1252-1262 ◽  
Author(s):  
Katharine Sedivy-Haley ◽  
Joshua Powles ◽  
Kenton Ko
Keyword(s):  
Alternative Splicing ◽  
Functional Significance ◽  
Protein Gene ◽  
Developmental Stages ◽  
Splice Variants ◽  
Cellular Processes ◽  
Rhomboid Proteases ◽  
Alternative Splice Variants ◽  
Arabidopsis Plant

Rhomboid proteases are involved in various cellular activities, from development to cancer, and cellular processes and substrates associated with rhomboid proteases or rhomboid-like proteins have been identified for a range of organisms. Plant rhomboid proteases or rhomboid-like proteins are the least understood of the group. Moreover, the general phenomenon of alternative splicing and rhomboid protein genes has yet to be studied robustly. This study thus focused on the alternative splicing events associated with the Arabidopsis rhomboid protein gene At1g25290. The patterns obtained through RT-PCR and DNA sequencing provided evidence of alternative splicing in the At1g25290 transcript population, especially in the region spanning exons 5 and 6. The levels of the two splice variants involving exons 5 and 6 appear to be sufficiently abundant to possess functional significance and appear to adjust relative to each other in different contexts. Adjustments were observed in tissues of different developmental stages, in an Arabidopsis plant bearing a mutation in another rhomboid protein, and in response to transgenic manipulations affecting the levels of Tic40, a plastid translocon component. The resulting change to the protein sequence may, in turn, affect how At1g25290 proteins interact with their substrates. Collectively, the evidence suggests that alternative splicing of At1g25290 bears functional significance in Arabidopsis.

scholarly journals Analysis of the Arabidopsis organellar rhomboid At1g74140 transcript population uncovered splicing patterns different from its close relative At1g74130

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1925
Author(s):  
Kenton Ko ◽  
Jeremy Guenther ◽  
Nicholas Ostan ◽  
Joshua Powles
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Splice Variants ◽  
The Other ◽  
Close Relative ◽  
Rt Pcr ◽  
Splicing Pattern ◽  
High Level ◽  
Splicing Patterns ◽  
Alternative Splice Variants

Background: Four distinct rhomboid genes appear to function in Arabidopsis plastids, two “active” types from the secretases and presenilin-like associated rhomboid-like (PARL) categories (At1g25290 and At5g25752) and two “inactive” rhomboid forms (At1g74130 and At1g74140).  The number of working rhomboids is further increased by alternative splicing, two reported for At1g25290 and three for At1g74130.  Since At1g25290 and At1g74130 exist as alternative splice variants, it would be necessary to assess the splicing patterns of the other two plastid rhomboid genes, At5g25752 and At1g74140, before studying the Arabidopsis plastid rhomboid system as a whole.   Methods: This study thus specifically focused on an analysis of the At1g74140 transcript population using various RT-PCR strategies.   Results: The exon mapping results indicate splicing patterns different from the close relative At1g74130, despite similarity between the exonic sequences.  The splicing patterns indicate a high level of sequence “discontinuity” in the At1g74140 transcript population with a significant portion of the discontinuity being generated by two regions of the gene.   Conclusion: The overall discontinuous splicing pattern of At1g74140 may be reflective of its mode of involvement in activities like controlling gene expression.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

scholarly journals Splicing Genomics Events in Cervical Cancer: Insights for Phenotypic Stratification and Biomarker Potency

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 130
Author(s):  
Flavia Zita Francies ◽  
Sheynaz Bassa ◽  
Aristotelis Chatziioannou ◽  
Andreas Martin Kaufmann ◽  
Zodwa Dlamini
Keyword(s):  
Cervical Cancer ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Splicing Factors ◽  
Aberrant Splicing ◽  
Molecular Alteration ◽  
Common Cancer ◽  
Potential Biomarkers

Gynaecological cancers are attributed to the second most diagnosed cancers in women after breast cancer. On a global scale, cervical cancer is the fourth most common cancer and the most common cancer in developing countries with rapidly increasing mortality rates. Human papillomavirus (HPV) infection is a major contributor to the disease. HPV infections cause prominent cellular changes including alternative splicing to drive malignant transformation. A fundamental characteristic attributed to cancer is the dysregulation of cellular transcription. Alternative splicing is regulated by several splicing factors and molecular changes in these factors lead to cancer mechanisms such as tumour development and progression and drug resistance. The serine/arginine-rich (SR) proteins and heterogeneous ribonucleoproteins (hnRNPs) have prominent roles in modulating alternative splicing. Evidence shows molecular alteration and expression levels in these splicing factors in cervical cancer. Furthermore, aberrant splicing events in cancer-related genes lead to chemo- and radioresistance. Identifying clinically relevant modifications in alternative splicing events and splicing variants, in cervical cancer, as potential biomarkers for their role in cancer progression and therapy resistance is scrutinised. This review will focus on the molecular mechanisms underlying the aberrant splicing events in cervical cancer that may serve as potential biomarkers for diagnosis, prognosis, and novel drug targets.

scholarly journals TAPAS: tools to assist the targeted protein quantification of human alternative splice variants

2014 ◽  
Vol 30 (20) ◽  
pp. 2989-2990 ◽  
Author(s):  
Jae-Seong Yang ◽  
Eduard Sabidó ◽  
Luis Serrano ◽  
Christina Kiel
Keyword(s):  
Alternative Splice ◽  
Splice Variants ◽  
Protein Quantification ◽  
Alternative Splice Variants

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

2008 ◽  
Vol 28 (13) ◽  
pp. 4320-4330 ◽  
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.

scholarly journals Mutation analysis and characterization of alternative splice variants of the Wilson disease gene ATP7B

Hepatology ◽  
2010 ◽  
Vol 52 (5) ◽  
pp. 1662-1670 ◽  
Author(s):  
Lei Wan ◽  
Chang-Hai Tsai ◽  
Chin-Moo Hsu ◽  
Chin-Chang Huang ◽  
Chih-Chao Yang ◽  
...  
Keyword(s):  
Alternative Splice ◽  
Mutation Analysis ◽  
Wilson Disease ◽  
Disease Gene ◽  
Splice Variants ◽  
Alternative Splice Variants

scholarly journals Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia

2020 ◽  
Author(s):  
Osvaldo D. Rivera ◽  
Michael J. Mallory ◽  
Mathieu Quesnel-Vallières ◽  
David C. Schultz ◽  
Martin Carroll ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Alternative Splicing ◽  
Myeloid Leukemia ◽  
Gene Disruption ◽  
Somatic Mutations ◽  
Aberrant Splicing ◽  
Gene Dysregulation ◽  
Number Of Patients ◽  
Acute Myeloid ◽  
Classical Mutation

AbstractMost genes associated with Acute Myeloid Leukemia (AML) are mutated in less than 10% of patients, suggesting alternative mechanisms for gene disruption contribute to this disease. Here we find a set of splicing events that disrupt the expression of a subset of AML-associated genes, including EZH2 and ZRSR2, independent of known somatic mutations. Most strikingly, in at least one cohort, aberrant splicing triples the number of patients with a reduction in functional EZH2 as compared to that predicted by somatic mutation of EZH2 alone. Together, these results demonstrate that classical mutation analysis underestimates the burden of functional gene disruption in AML and highlights the importance of assessing the contribution of alternative splicing to gene dysregulation in human disease.

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