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 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 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 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.

Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Cognitive Processes ◽  
Evolutionary History ◽  
Behavioral Responses ◽  
History Of ◽  
Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

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