Alternative splicing: current perspectives

Kim, Eddo; Goren, Amir; Ast, Gil

doi:10.1002/bies.20692

Cited by 201 publications

(179 citation statements)

References 112 publications

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“…Four modes of alternative splicing are generally observed: (1) exon skipping, (2) mutually exclusive exon usage, (3) alternative splice site selection, and (4) intron retention ( Figure 3A). Exon skipping, the most prevalent form of alternative splicing in higher eukaryotes, 20 denotes the excision of ≥1 exons and its surrounding introns from a pre-mRNA. Mutually exclusive exon usage represents a form of exon skipping where either one or another exon, but never both, is included in the mature mRNA.…”

Section: Different Types Of Alternative Splicingmentioning

confidence: 99%

RNA Splicing

Hoogenhof

Pinto

Creemers

2016

Circulation Research

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RNA splicing, a post-transcriptional process necessary to form a mature mRNA, was discovered in the late 1970s. 1 Two different modes of splicing have been defined, that is, constitutive splicing and alternative splicing. Constitutive splicing is the process of removing introns from the premRNA, and joining the exons together to form a mature mRNA. Alternative splicing, on the other hand, is the process where exons can be included or excluded in different combinations to create a diverse array of mRNA transcripts from a single pre-mRNA and therefore serves as a process to increase the diversity of the transcriptome. The estimated number of alternative splicing events in the human transcriptome has risen sharply over the past decades. In the 1980s, it was thought that about 5% of human genes were subjected to alternative splicing.2 In 2002, this number had risen to 60%, 3 and now, after implementation of next-generation-sequencing technologies, we know that the vast majority, >95% of mRNAs, are subjected to alternative splicing. 4 Nevertheless, the function of a large fraction of these splice isoforms remains to be elucidated. Furthermore, it is anticipated that in different tissues, or in tissues with different disease states, new isoforms still remain to be identified. 5The process of splicing is highly conserved during evolution. Splicing is more prevalent in multicellular than in unicellular eukaryotes because of the lower number of introncontaining genes in the latter. 6 Later in evolution, alternative splicing becomes more prevalent in vertebrates than in invertebrates. Interestingly, just a single exon-skipping event in the RNA-binding protein (RBP), polypyrimidine tract binding protein 1 has been shown to direct numerous alternative splicing changes between species, indicating that a single splicing event can amplify transcriptome diversity between species. 7The recent observation that the total number of protein-coding genes does not differ much between species, fueled the hypothesis that alternative splicing largely contributes to organism diversity. And indeed, as we move up the phylogenetic tree, alternative splicing complexity increases, with the highest complexity in primates. 8,9The aim of this review is to give a comprehensive overview of all aspects of constitutive and alternative splicing and their regulators, as well as the importance of these different aspects in human disease, with a focus on the heart. In addition, we discuss possible therapeutic interventions and try to uncover potential future directions of research. Major and Minor SpliceosomeRNA splicing is performed by the spliceosome, a large and dynamic ribonucleoprotein complex composed of proteins and small nuclear RNAs (snRNAs), which assembles on the pre-mRNA (Figure 1). Ribonucleoproteins consist of 1 or 2 small nuclear RNAs (snRNAs; U1, U2, U4/U6, or U5), and a variable number of complex-specific proteins.

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Section: Different Types Of Alternative Splicingmentioning

confidence: 99%

RNA Splicing

Hoogenhof

Pinto

Creemers

2016

Circulation Research

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“…Figure 3 showed that the diversity found in intron 2 region of the GHRH gene. Intron is an internal space between protein-coding bases and will disappear during the process of transcription or splicing (Kim et al, 2007).…”

Section: Ghrh|haeiii Ge�e Polymorph�smmentioning

confidence: 99%

GHRH|HaeIII Gene Polymorphism in Dairy and Beef Cattle at National Livestock Breeding Centers

Rini¹,

Sumantri²,

Anggraini³

2013

Med Pet

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ABSTRACT), kecuali pada sapi FH di BIB Lembang, sapi Brahman, dan Angus di BET Cipelang. Nilai heterozigositas tertinggi adalah 0,471 untuk sapi FH pejantan di BIB Lembang, sebaliknya, nilai terendah adalah 0,344 untuk sapi FH pejantan di BBIB Singosari. Nilai heterozigositas sapi FH lebih rendah daripada sapi Simmental dan Limousin. Gen GHRH pada sapi FH dan sapi pedaging menunjukkan polimorfik, kecuali pada sapi Brahman yang hanya memiliki alel B.

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“…This process is mediated by a dynamic and flexible macromolecular machine, the spliceosome, which works in a synergistic and antistatic manner (as explained below) (6,7). Three possible mechanisms, exon shuffling, exonization of transposable elements and constitutively spliced exons, have been proposed for the origin of alternative splicing (8).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of alternative splicing and its regulation

et al. 2014

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Abstract. Alternative splicing of precursor mRNA is an essential mechanism to increase the complexity of gene expression, and it plays an important role in cellular differentiation and organism development. Regulation of alternative splicing is a complicated process in which numerous interacting components are at work, including cis-acting elements and trans-acting factors, and is further guided by the functional coupling between transcription and splicing. Additional molecular features, such as chromatin structure, RNA structure and alternative transcription initiation or alternative transcription termination, collaborate with these basic components to generate the protein diversity due to alternative splicing.

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Alternative splicing: current perspectives

Cited by 201 publications

References 112 publications

RNA Splicing

RNA Splicing

GHRH|HaeIII Gene Polymorphism in Dairy and Beef Cattle at National Livestock Breeding Centers

Mechanism of alternative splicing and its regulation

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