scholarly journals Functional roles of protein splicing factors

2012 ◽  
Vol 32 (4) ◽  
pp. 345-359 ◽  
Author(s):  
Hsin-Chou Chen ◽  
Soo-Chen Cheng
Keyword(s):  
Rna Splicing ◽  
Structural Changes ◽  
Dynamic Structure ◽  
Splicing Factors ◽  
Protein Splicing ◽  
Rna Helicases ◽  
Functional Roles ◽  
Assembly Pathway ◽  
Small Nuclear Rnas ◽  
Sequential Binding

RNA splicing is one of the fundamental processes in gene expression in eukaryotes. Splicing of pre-mRNA is catalysed by a large ribonucleoprotein complex called the spliceosome, which consists of five small nuclear RNAs and numerous protein factors. The spliceosome is a highly dynamic structure, assembled by sequential binding and release of the small nuclear RNAs and protein factors. DExD/H-box RNA helicases are required to mediate structural changes in the spliceosome at various steps in the assembly pathway and have also been implicated in the fidelity control of the splicing reaction. Other proteins also play key roles in mediating the progression of the spliceosome pathway. In this review, we discuss the functional roles of the protein factors involved in the spliceosome pathway primarily from studies in the yeast system.

scholarly journals Splicing at the phase-separated nuclear speckle interface: a model

2020 ◽  
Author(s):  
Susan E Liao ◽  
Oded Regev
Keyword(s):  
Phase Separation ◽  
Rna Splicing ◽  
Splicing Factors ◽  
Sequence Motifs ◽  
Splice Sites ◽  
Nuclear Speckles ◽  
Nuclear Speckle ◽  
Functional Roles ◽  
Hnrnp Proteins ◽  
Model Sequence

Abstract Phase-separated membraneless bodies play important roles in nucleic acid biology. While current models for the roles of phase separation largely focus on the compartmentalization of constituent proteins, we reason that other properties of phase separation may play functional roles. Specifically, we propose that interfaces of phase-separated membraneless bodies could have functional roles in spatially organizing biochemical reactions. Here we propose such a model for the nuclear speckle, a membraneless body implicated in RNA splicing. In our model, sequence-dependent RNA positioning along the nuclear speckle interface coordinates RNA splicing. Our model asserts that exons are preferentially sequestered into nuclear speckles through binding by SR proteins, while introns are excluded through binding by nucleoplasmic hnRNP proteins. As a result, splice sites at exon-intron boundaries are preferentially positioned at nuclear speckle interfaces. This positioning exposes splice sites to interface-localized spliceosomes, enabling the subsequent splicing reaction. Our model provides a simple mechanism that seamlessly explains much of the complex logic of splicing. This logic includes experimental results such as the antagonistic duality between splicing factors, the position dependence of splicing sequence motifs, and the collective contribution of many motifs to splicing decisions. Similar functional roles for phase-separated interfaces may exist for other membraneless bodies.

scholarly journals Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 923
Author(s):  
Koji Kitamura ◽  
Keisuke Nimura
Keyword(s):  
Dna Sequences ◽  
Rna Splicing ◽  
Splicing Factors ◽  
Splicing Regulation ◽  
Aberrant Splicing ◽  
Aberrant Expression ◽  
Non Coding Rnas ◽  
Precursor Mrna ◽  
Splicing Enhancer ◽  
Small Nuclear Ribonucleoproteins

RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5’ and 3’ splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.

scholarly journals AN ALTERNATIVE APPROACH OF INPUT-OUTPUT TABLES TO DYNAMIC STRUCTURE CHANGES IN KOREAN IT INDUSTRIES

2013 ◽  
Vol 19 (2) ◽  
pp. 257-271 ◽  
Author(s):  
Byung-Sun Cho ◽  
Sang Sup Cho ◽  
Jungmann Lee
Keyword(s):  
Structural Changes ◽  
Impact Analysis ◽  
Consumer Preferences ◽  
New Technology ◽  
Dynamic Structure ◽  
Input Output ◽  
It Industry ◽  
Current Time ◽  
Structure Changes ◽  
Industry Policy

The structure of the IT industry has always evolved in line with technological progresses and changes in consumer preferences, as well as with regulatory trends. This is why, when assessing the effect that a new technology or industry policy may have on the national economy, companies and policy-makers need to consider dynamic structural changes affecting the IT industry. One of the most popular existing methods for economic impact analysis is based on a traditional input-output table, and is conducted over a period between the current time and a given time in the future. In this study, we compare the accuracy of RAS and Cross Entropy (CE), the two most widely employed methods for updating input-output (IO) tables, by applying them to Korean IT industries. The main results of this study are the following. In terms of the accuracy of input coefficient estimates, we have found that both the RAS and CE methods have a tendency to overestimate or underestimate them. When the Korean industry was first divided into fourteen sectors, and the RAS and CE methods were applied to each of the fourteen industries, it was difficult to discern a consistent trend for the two methods concerning their accuracy in estimation of input coefficients. Secondly, when used to update an IO table in which the IT industry is subdivided into IT equipment and services, neither the CE nor RAS method proved distinctly superior to the other. Third, in light of the above two findings, we concluded that updating IO tables is best done through a hybrid method combining the CE and RAS methods. This paper proposes a procedure consisting of two steps: IO tables are first updated using the two methods, which are once again updated by employing the OLS average approach through the use of optimal weights.

scholarly journals CTNNBL1 Is a Novel Nuclear Localization Sequence-binding Protein That Recognizes RNA-splicing Factors CDC5L and Prp31

2011 ◽  
Vol 286 (19) ◽  
pp. 17091-17102 ◽  
Author(s):  
Karuna Ganesh ◽  
Salome Adam ◽  
Benjamin Taylor ◽  
Paul Simpson ◽  
Cristina Rada ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Rna Splicing ◽  
Binding Protein ◽  
Nuclear Localization Sequence ◽  
Splicing Factors ◽  
Localization Sequence

scholarly journals Secondary Structural Model of Human MALAT1 Reveals Multiple Structure–Function Relationships

2019 ◽  
Vol 20 (22) ◽  
pp. 5610 ◽  
Author(s):  
Phillip J. McCown ◽  
Matthew C. Wang ◽  
Luc Jaeger ◽  
Jessica A. Brown
Keyword(s):  
Structure Function ◽  
Noncoding Rna ◽  
Structural Model ◽  
Dynamic Structure ◽  
Nucleotide Polymorphisms ◽  
Rna Structures ◽  
Rna Modifications ◽  
Functional Roles ◽  
Conserved Core

Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an abundant nuclear-localized long noncoding RNA (lncRNA) that has significant roles in cancer. While the interacting partners and evolutionary sequence conservation of MALAT1 have been examined, much of the structure of MALAT1 is unknown. Here, we propose a hypothetical secondary structural model for 8425 nucleotides of human MALAT1 using three experimental datasets that probed RNA structures in vitro and in various human cell lines. Our model indicates that approximately half of human MALAT1 is structured, forming 194 helices, 13 pseudoknots, five structured tetraloops, nine structured internal loops, and 13 intramolecular long-range interactions that give rise to several multiway junctions. Evolutionary conservation and covariation analyses support 153 of 194 helices in 51 mammalian MALAT1 homologs and 42 of 194 helices in 53 vertebrate MALAT1 homologs, thereby identifying an evolutionarily conserved core that likely has important functional roles in mammals and vertebrates. Data mining revealed that RNA modifications, somatic cancer-associated mutations, and single-nucleotide polymorphisms may induce structural rearrangements that sequester or expose binding sites for several cancer-associated microRNAs. Our findings reveal new mechanistic leads into the roles of MALAT1 by identifying several intriguing structure–function relationships in which the dynamic structure of MALAT1 underlies its biological functions.

Spatial and Temporal Expression of Cold-responsive DEAD-box RNA Helicases Reveals their Functional Roles During Embryogenesis in Arabidopsis thaliana

2011 ◽  
Vol 29 (4) ◽  
pp. 761-768 ◽  
Author(s):  
Swamy K. Tripurani ◽  
Kentaro Nakaminami ◽  
Kari B. Thompson ◽  
Samuel V. Crowell ◽  
Charles L. Guy ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Temporal Expression ◽  
Rna Helicases ◽  
Functional Roles ◽  
Dead Box

scholarly journals Elucidation of the 14-3-3ζ interactome reveals critical roles of RNA-splicing factors during adipogenesis

2018 ◽  
Vol 293 (18) ◽  
pp. 6736-6750 ◽  
Author(s):  
Yves Mugabo ◽  
Mina Sadeghi ◽  
Nancy N. Fang ◽  
Thibault Mayor ◽  
Gareth E. Lim
Keyword(s):  
Rna Splicing ◽  
Splicing Factors

scholarly journals Aberrant RNA Splicing in Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 167-185 ◽  
Author(s):  
Luisa Escobar-Hoyos ◽  
Katherine Knorr ◽  
Omar Abdel-Wahab
Keyword(s):  
Small Molecules ◽  
Rna Splicing ◽  
Clinical Development ◽  
Splicing Factors ◽  
Global Changes ◽  
Splicing Regulation ◽  
Enzymatic Process ◽  
Patients With Cancer ◽  
Aberrant Rna

RNA splicing, the enzymatic process of removing segments of premature RNA to produce mature RNA, is a key mediator of proteome diversity and regulator of gene expression. Increased systematic sequencing of the genome and transcriptome of cancers has identified a variety of means by which RNA splicing is altered in cancer relative to normal cells. These findings, in combination with the discovery of recurrent change-of-function mutations in splicing factors in a variety of cancers, suggest that alterations in splicing are drivers of tumorigenesis. Greater characterization of altered splicing in cancer parallels increasing efforts to pharmacologically perturb splicing and early-phase clinical development of small molecules that disrupt splicing in patients with cancer. Here we review recent studies of global changes in splicing in cancer, splicing regulation of mitogenic pathways critical in cancer transformation, and efforts to therapeutically target splicing in cancer.

scholarly journals ALG-1 Influences Accurate mRNA Splicing Patterns in the Caenorhabditis elegans Intestine and Body Muscle Tissues by Modulating Splicing Factor Activities

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 931-951 ◽  
Author(s):  
Kasuen Kotagama ◽  
Anna L. Schorr ◽  
Hannah S. Steber ◽  
Marco Mangone
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Splicing ◽  
Specific Gene ◽  
Splicing Factors ◽  
Tissue Specific ◽  
Link Type ◽  
Body Muscle ◽  
Mirna Targets ◽  
Mirna Pathway

MicroRNAs (miRNAs) are known to modulate gene expression, but their activity at the tissue-specific level remains largely uncharacterized. To study their contribution to tissue-specific gene expression, we developed novel tools to profile putative miRNA targets in the Caenorhabditis elegans intestine and body muscle. We validated many previously described interactions and identified ∼3500 novel targets. Many of the candidate miRNA targets curated are known to modulate the functions of their respective tissues. Within our data sets we observed a disparity in the use of miRNA-based gene regulation between the intestine and body muscle. The intestine contained significantly more putative miRNA targets than the body muscle highlighting its transcriptional complexity. We detected an unexpected enrichment of RNA-binding proteins targeted by miRNA in both tissues, with a notable abundance of RNA splicing factors. We developed in vivo genetic tools to validate and further study three RNA splicing factors identified as putative miRNA targets in our study (asd-2, hrp-2, and smu-2), and show that these factors indeed contain functional miRNA regulatory elements in their 3′UTRs that are able to repress their expression in the intestine. In addition, the alternative splicing pattern of their respective downstream targets (unc-60, unc-52, lin-10, and ret-1) is dysregulated when the miRNA pathway is disrupted. A reannotation of the transcriptome data in C. elegans strains that are deficient in the miRNA pathway from past studies supports and expands on our results. This study highlights an unexpected role for miRNAs in modulating tissue-specific gene isoforms, where post-transcriptional regulation of RNA splicing factors associates with tissue-specific alternative splicing.

Sign in / Sign up

Export Citation Format

Share Document