scholarly journals A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration

2022 ◽  
Author(s):  
Yichang Jia
Keyword(s):  
Rna Binding ◽  
Rna Binding Protein ◽  
Conditional Knockout ◽  
Interacting Protein ◽  
U2 Snrna ◽  
Mrna Pool ◽  
Splicing Efficiency ◽  
Underlying Mechanisms ◽  
Molecular Brake ◽  
Polyadenylated Mrna

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at Bact 29 state, an active spliceosome but not catalytically primed, which depends on SNIP1 (Smad Nuclear Interacting Protein 1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact component preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake for the spliceosome pausing, and that its misregulation contributes to neurodegeneration.

scholarly journals Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein geneCirbp

2016 ◽  
Vol 30 (17) ◽  
pp. 2005-2017 ◽  
Author(s):  
Ivana Gotic ◽  
Saeed Omidi ◽  
Fabienne Fleury-Olela ◽  
Nacho Molina ◽  
Felix Naef ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Splicing Efficiency

The RNA-binding protein FUS/TLS is a common aggregate-interacting protein in polyglutamine diseases

2010 ◽  
Vol 66 (1) ◽  
pp. 131-133 ◽  
Author(s):  
Hiroshi Doi ◽  
Shigeru Koyano ◽  
Yume Suzuki ◽  
Nobuyuki Nukina ◽  
Yoshiyuki Kuroiwa
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Polyglutamine Diseases ◽  
Interacting Protein

scholarly journals Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B

2017 ◽  
Author(s):  
Chih-Yung S. Lee ◽  
Tu Lu ◽  
Geraldine Seydoux
Keyword(s):  
Transcription Factor ◽  
Germ Cells ◽  
Rna Binding ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Rna Binding Protein ◽  
Dependent Manner ◽  
Embryonic Cells ◽  
C Elegans ◽  
Underlying Mechanisms

AbstractThe Nanos RNA-binding protein has been implicated in the specification of primordial germ cells (PGCs) in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 iC. elegans. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of PGCs away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity.

scholarly journals A Novel Double-stranded RNA-binding Protein, Disco Interacting Protein 1 (DIP1), Contributes to Cell Fate Decisions duringDrosophilaDevelopment

2003 ◽  
Vol 278 (39) ◽  
pp. 38040-38050 ◽  
Author(s):  
Dorothy DeSousa ◽  
Mahua Mukhopadhyay ◽  
Peter Pelka ◽  
Xiaoli Zhao ◽  
Bijan K. Dey ◽  
...  
Keyword(s):  
Cell Fate ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Interacting Protein ◽  
Double Stranded Rna ◽  
Cell Fate Decisions

scholarly journals Conditional Knockout of the RNA-Binding Protein HuR in CD4+ T Cells Reveals a Gene Dosage Effect on Cytokine Production

2014 ◽  
Vol 20 (1) ◽  
pp. 93-108 ◽  
Author(s):  
Matthew M. Gubin ◽  
Patsharaporn Techasintana ◽  
Joseph D. Magee ◽  
Garrett M. Dahm ◽  
Robert Calaluce ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Rna Binding ◽  
Cytokine Production ◽  
Gene Dosage ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Dosage Effect ◽  
Conditional Knockout ◽  
Gene Dosage Effect

scholarly journals An RNA Switch of a Large Exon of Ninein Is Regulated by the Neural Stem Cell Specific-RNA Binding Protein, Qki5

2019 ◽  
Vol 20 (5) ◽  
pp. 1010 ◽  
Author(s):  
Yoshika Hayakawa-Yano ◽  
Masato Yano
Keyword(s):  
Alternative Splicing ◽  
High Throughput Sequencing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Neural Progenitor Cell ◽  
Conditional Knockout ◽  
Splicing Factors ◽  
Axon Development ◽  
Rna Switch

A set of tissue-specific splicing factors are thought to govern alternative splicing events during neural progenitor cell (NPC)-to-neuron transition by regulating neuron-specific exons. Here, we propose one such factor, RNA-binding protein Quaking 5 (Qki5), which is specifically expressed in the early embryonic neural stem cells. We performed mRNA-SEQ (Sequence) analysis using mRNAs obtained by developing cerebral cortices in Qk (Quaking) conditional knockout (cKO) mice. As expected, we found a large number of alternative splicing changes between control and conditional knockouts relative to changes in transcript levels. DAVID (The Database for Annotation, Visualization and Integrated Discovery) and Metascape analyses suggested that the affected spliced genes are involved in axon development and microtubule-based processes. Among these, the mRNA coding for the Ninein protein is listed as one of Qki protein-dependent alternative splicing targets. Interestingly, this exon encodes a very long polypeptide (2121 nt), and has been previously defined as a dynamic RNA switch during the NPC-to-neuron transition. Additionally, we validated that the regulation of this large exon is consistent with the Qki5-dependent alternative exon inclusion mode suggested by our previous Qki5 HITS-CLIP (high throughput sequencing-cross linking immunoprecipitation) analysis. Taken together, these data suggest that Qki5 is an important factor for alternative splicing in the NPC-to-neuron transition.

149. TRANSLATIONAL CONTROL IN FOLLICULOGENESIS AND OOCYTE DEVELOPMENT: A ROLE FOR RNA-BINDING PROTEIN MUSASHI-1

2010 ◽  
Vol 22 (9) ◽  
pp. 67
Author(s):  
K. M. Gunter ◽  
B. A. Fraser ◽  
A. P. Sobinoff ◽  
V. Pye ◽  
N. A. Siddall ◽  
...  
Keyword(s):  
Translational Control ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Oocyte Development ◽  
Cell Cycle Regulators ◽  
Translational Repressor ◽  
Qpcr Analysis ◽  
Mrna Pool ◽  
Rna Immunoprecipitation

Control of the maternal mRNA pool during oocyte maturation is crucial to the correct temporal and spatial expression of proteins, particularly during oocyte transcriptional quiescence. We have identified Musashi-1 as being present within the oocyte/ovary, where this RNA-binding protein is believed to act as a translational repressor of target mRNAs. Recent studies in mammalian neural and intestinal systems have identified a number of cell cycle regulators as potential targets of Msi-1. Using Msi-1 protein-RNA immunoprecipitation, we have also identified musashi-2 (msi-2) and c-mos as putative targets in the mouse oocyte. To further study these targets, a transgenic mouse was produced to overexpress Msi-1 exclusively in the oocyte. QPCR analysis, performed on intact ovaries of wild type (WT) and Tg mice, confirmed a 1.5-fold increase in msi-1 expression in tgMsi-1/+ ovaries in excess of WT ovary expression. QPCR analysis of Msi-1 target expression, performed on intact WT and Tg ovaries, in conjunction with transcript obtained from the Msi-1 protein-RNA immunoprecipitation, revealed an overall increase in expression in the tgMsi-1/+ and Msi-1 IP samples, respectively, of p21WAF-1 (~2.5-fold; undetected), cdkn2a (~2-fold; undetected), notch1 (~3-fold;undetected), c-mos (no difference; ~41-fold) and msi-2 (~7-fold; ~10-fold). Immunohistochemical analysis of Msi-2 protein expression in transgenic juvenile mouse ovaries,demonstrated a decrease in expression of Msi-2 in tgMsi-1/+ ovaries, when compared to WT ovary expression, suggesting that Msi-2 mRNA is translationally repressed by Msi-1. Therefore, preliminary analysis suggests that Msi-1 may play a role inregulating transcripts of genes necessary for processes characteristic of meiotic progression and oocyte development.

scholarly journals Hox Transcription Factor Ultrabithorax Ib Physically and Genetically Interacts with Disconnected Interacting Protein 1, a Double-stranded RNA-binding Protein

2004 ◽  
Vol 279 (25) ◽  
pp. 26433-26444 ◽  
Author(s):  
Sarah E. Bondos ◽  
Daniel J. Catanese ◽  
Xin-Xing Tan ◽  
Alicia Bicknell ◽  
Likun Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Interacting Protein ◽  
Double Stranded Rna

scholarly journals RNA-binding Protein TLS Is a Major Nuclear Aggregate-interacting Protein in Huntingtin Exon 1 with Expanded Polyglutamine-expressing Cells

2007 ◽  
Vol 283 (10) ◽  
pp. 6489-6500 ◽  
Author(s):  
Hiroshi Doi ◽  
Kazumasa Okamura ◽  
Peter O. Bauer ◽  
Yoshiaki Furukawa ◽  
Hideaki Shimizu ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Interacting Protein ◽  
Exon 1
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