scholarly journals FUNCTIONAL UNDERSTANDING OF THE DIVERSE EXON–INTRON STRUCTURES OF HUMAN GPCR GENES

2014 ◽  
Vol 12 (01) ◽  
pp. 1350019 ◽  
Author(s):  
DOROTHY A. HAMMOND ◽  
VICTOR OLMAN ◽  
YING XU
Keyword(s):  
Alternative Splicing ◽  
Statistical Significance ◽  
Protein Isoforms ◽  
P Value ◽  
Protein Splicing ◽  
Functional Protein ◽  
Functional Understanding ◽  
Specific Alternative ◽  
Splicing Isoforms ◽  
Adjacent Exon

The GPCR genes have a variety of exon–intron structures even though their proteins are all structurally homologous. We have examined all human GPCR genes with at least two functional protein isoforms, totaling 199, aiming to gain an understanding of what may have contributed to the large diversity of the exon–intron structures of the GPCR genes. The 199 genes have a total of 808 known protein splicing isoforms with experimentally verified functions. Our analysis reveals that 1301 (80.6%) adjacent exon–exon pairs out of the total of 1,613 in the 199 genes have either exactly one exon skipped or the intron in-between retained in at least one of the 808 protein splicing isoforms. This observation has a statistical significance p-value of 2.051762 * e-09, assuming that the observed splicing isoforms are independent of the exon–intron structures. Our interpretation of this observation is that the exon boundaries of the GPCR genes are not randomly determined; instead they may be selected to facilitate specific alternative splicing for functional purposes.

scholarly journals DoChaP: The Domain Change Presenter

2020 ◽  
Author(s):  
Shani T. Gal-Oz ◽  
Nimrod Haiat ◽  
Dana Eliyahu ◽  
Guy Shani ◽  
Tal Shay
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Protein Domains ◽  
Visual Presentation ◽  
Structural Effect ◽  
Protein Isoforms ◽  
Multiple Transcripts ◽  
Genome Wide ◽  
Health And Disease ◽  
Specific Alternative

AbstractAlternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon–domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain–exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon–domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.

scholarly journals isoTarget: a genetic method for analyzing the functional diversity of splicing isoforms in vivo

2020 ◽  
Author(s):  
Hao Liu ◽  
Sarah Pizzano ◽  
Ruonan Li ◽  
Wenquan Zhao ◽  
Macy W. Veling ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Biochemical Properties ◽  
Protein Isoforms ◽  
Genetic Method ◽  
Axon Development ◽  
Splicing Isoforms ◽  
Multi Level ◽  
The Difference ◽  
Endogenous Proteins

SUMMARYProtein isoforms generated by alternative splicing contribute to proteome diversity. Due to the lack of effective techniques, isoform-specific functions, expression, localization, and signaling mechanisms of endogenous proteins in vivo are unknown for most genes. Here we report a genetic method, termed isoTarget, for blocking the expression of a targeted isoform without affecting the other isoforms and for conditional tagging the targeted isoform for multi-level analyses in select cells. Applying isoTarget to two mutually exclusive isoforms of Drosophila Dscam, Dscam[TM1] and [TM2], we found that endogenous Dscam[TM1] is localized in dendrites while Dscam[TM2] is in both dendrites and axons. We demonstrate that the difference in subcellular localization between Dscam[TM1] and [TM2], rather than any difference in biochemical properties, leads to the two isoforms’ differential contributions to dendrite and axon development. Moreover, with isoTarget, we discovered that the subcellular enrichment of functional partners results in a DLK/Wallenda-Dscam[TM2]-Dock signaling cascade specifically in axons. isoTarget is an effective technique for studying how alternative splicing enhances proteome complexity.

scholarly journals Transcripts' evolutionary history and structural dynamics give mechanistic insights into the functional diversity of the JNK family.

2017 ◽  
Author(s):  
Adel Ait-hamlat ◽  
Diego Javier Zea ◽  
Antoine Labeeuw ◽  
Lelia Polit ◽  
Hugues Richard ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Structural Dynamics ◽  
Evolutionary History ◽  
Protein Isoforms ◽  
Computational Tool ◽  
Tertiary Structures ◽  
Transcript Isoforms ◽  
History Of ◽  
Transcription Sites ◽  
Splicing Isoforms

Alternative splicing and alternative initiation/termination transcription sites, have the potential to greatly expand the proteome in eukaryotes by producing several transcript isoforms from the same gene. Although these mechanisms are well described at the genomic level, little is known about their contribution to protein evolution and their impact at the protein structure level. Here, we address both issues by reconstructing the evolutionary history of transcripts and by modeling the tertiary structures of the corresponding protein isoforms. We reconstruct phylogenetic forests relating 60 transcripts from the c-Jun N-terminal kinase (JNK) family observed in 7 species. We identify two alternative splicing events of ancient origin and show that they induce subtle changes on the protein's structural dynamics. We highlight a previously uncharacterized transcript whose predicted structure seems stable in solution. We further demonstrate that orphan transcripts, for which no phylogeny could be reconstructed, display peculiar sequence and structural properties. Our approach is implemented in PhyloSofS (Phylogenies of Splicing Isoforms Structures), a fully automated computational tool freely available at https://github.com/PhyloSofS-Team/PhyloSofS.

scholarly journals Distribution of alternative untranslated regions within the mRNA of the CELF1 splicing factor affects its expression

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Arkadiusz Kajdasz ◽  
Daria Niewiadomska ◽  
Michal Sekrecki ◽  
Krzysztof Sobczak
Keyword(s):  
Alternative Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Striated Muscle ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Protein Isoforms ◽  
Untranslated Regions ◽  
Splicing Isoforms

AbstractCUG-binding protein, ELAV-like Family Member 1 (CELF1) plays an important role during the development of different tissues, such as striated muscle and brain tissue. CELF1 is an RNA-binding protein that regulates RNA metabolism processes, e.g., alternative splicing, and antagonizes other RNA-binding proteins, such as Muscleblind-like proteins (MBNLs). Abnormal activity of both classes of proteins plays a crucial role in the pathogenesis of myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults. In this work, we show that alternative splicing of exons forming both the 5′ and 3′ untranslated regions (UTRs) of CELF1 mRNA is efficiently regulated during development and tissue differentiation and is disrupted in skeletal muscles in the context of DM1. Alternative splicing of the CELF1 5′UTR leads to translation of two potential protein isoforms that differ in the lengths of their N-terminal domains. We also show that the MBNL and CELF proteins regulate the distribution of mRNA splicing isoforms with different 5′UTRs and 3′UTRs and affect the CELF1 expression by changing its sensitivity to specific microRNAs or RNA-binding proteins. Together, our findings show the existence of different mechanisms of regulation of CELF1 expression through the distribution of various 5′ and 3′ UTR isoforms within CELF1 mRNA.

SERUM PROLACTINE LEVEL IN PATIENTS OF PSORIASIS VULGARIS AND ITS CORRELATION WITH DISEASE SEVERITY: A CASE-CONTROL STUDY

2019 ◽  
Vol 3 (6) ◽  
Author(s):  
Pawan Kumar Saini ◽  
Devendra Yadav ◽  
Rozy Badyal ◽  
Suresh Jain ◽  
Arti Singh ◽  
...  
Keyword(s):  
Disease Severity ◽  
Prolactin Level ◽  
Case Control Study ◽  
Statistical Significance ◽  
Case Control ◽  
Serum Prolactin ◽  
P Value ◽  
Serum Prolactin Level ◽  
R Value ◽  
Control Study

Background: Psoriasis is an autoimmune chronic inflammatory disorder affecting the skin mediated by T-lymphocytes resulting in production of cytokines which cause hyperproliferation of keratinocytes.  Several factors and hormones like Prolactin have an action similar to these cytokines in promoting the multiplication of keratinocytes and other cells like lymphocytes and epithelial cells may have a role on the etiopathogenesis of psoriasis. Aim:-The aim of study is to compare the serum Prolactin levels in patients of psoriasis with a control group. Setting and study design: This is a case-control study conducted in the department of Dermatology, Venereology and Leprosy GMC, Kota over a period of 1year from July 2017 to June 2018 Material and method: The study included 100 cases of psoriasis (60 males and 40 females) and 100 controls similar for age and sex. Serum Prolactin levels were measured by ECLIA and results were obtained. Statistical analysis: Mean and standard deviation were calculated for each variable. Statistical significance of the results was analyzed using correlation analysis (Pearson correlation coefficient) and independent samples t-test. Statistical significance was assumed at p value<0.05. Result: Serum Prolactin level was significantly higher in cases of psoriasis compared to controls (p-value <0.001). PASI score and serum Prolactin levels were found to have a positive correlation (r value = 0.337; p-value: 0.001). No significant  correlation was found between serum levels of Prolactin and duration of disease r value= -0.034, P value =0.733). Serum Prolactin level was higher in male patients compared to females patients. Conclusion:- High serum Prolactin may be a biological marker of disease severity in psoriasis and may have a role in the pathogenesis of psoriasis. Further studies with large sample size are required to confirm this hypothesis.

Awareness of radiation doses and risks among radiology residents, fellows, specialists, consultants and technologists in Jeddah, Saudi Arabia: Cross-Sectional Study. (Preprint)

2019 ◽  
Author(s):  
Bashayer Hassan Shuaib ◽  
Rahaf Hisham Niazi ◽  
Ahmed Haitham Abduljabbar ◽  
Mohammed Abdulraheem Wazzan
Keyword(s):  
Interventional Radiology ◽  
Ionizing Radiation ◽  
Statistical Significance ◽  
Knowledge Score ◽  
P Value ◽  
Radiation Doses ◽  
Cross Sectional ◽  
The Right ◽  
Interventional Radiology Procedures ◽  
Radiology Staff

BACKGROUND Radiology now plays a major role to diagnose, monitoring, and management of several diseases; numerous diagnostic and interventional radiology procedures involve exposure to ionizing radiation. Radiology now plays a major role to diagnose, monitoring, and management of several diseases; numerous diagnostic and interventional radiology procedures involve exposure to ionizing radiation. OBJECTIVE This study aimed to discover and compare the awareness level of radiation doses, protection issues, and risks among radiology staff in Jeddah hospitals. METHODS A cross-sectional survey containing 25 questions on personal information and various aspects of radiation exposure doses and risks was designed using an online survey tool and the link was emailed to all radiology staff in eight tertiary hospitals in Jeddah. The authors were excluded from the study. A P-value of < .05 was used to identify statistical significance. All analyses were performed using SPSS, version 21. RESULTS Out of 156 participants the majority 151 (96.8%) had poor knowledge score, where the mean scores were 2.4±1.3 for doses knowledge, 2.1±1.1for cancer risks knowledge, 2.3±0.6 for general information, and 6.7±1.9 for the total score. Only 34.6% of the participants were aware of the dosage of a single-view chest x-ray, and 9.0% chose the right answer for the approximate effective dose received by a patient in a two-view. 42.9% were able to know the correct dose of CT abdomen single phase. There is a significant underestimation of cancer risk of CT studies especially for CT abdomen where only 23.7% knew the right risk. A p-value of <0.05 was used to identify statistical significance. No significant difference of knowledge score was detected regarding gender (P =.2) or work position (P=.66). CONCLUSIONS Our survey results show considerable inadequate knowledge in all groups without exception. We recommended a conscientious effort to deliver more solid education and obtain more knowledge in these matters and providing periodic training courses to teach how to minimize the dose of radiation and to avoid risk related. CLINICALTRIAL not applicable

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