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

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.

2007 ◽  
Vol 176 (7) ◽  
pp. 929-939 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Tilman Achsel ◽  
Autumn Massiello ◽  
Charles E. Chalfant ◽  
Claudio Sette

The RNA-binding protein Sam68 is involved in apoptosis, but its cellular mRNA targets and its mechanism of action remain unknown. We demonstrate that Sam68 binds the mRNA for Bcl-x and affects its alternative splicing. Depletion of Sam68 by RNA interference caused accumulation of antiapoptotic Bcl-x(L), whereas its up-regulation increased the levels of proapoptotic Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. A point mutation in the RNA-binding domain of Sam68 influenced its splicing activity and subnuclear localization. Moreover, coexpression of ASF/SF2 with Sam68, or fusion with an RS domain, counteracted Sam68 splicing activity toward Bcl-x. Finally, Sam68 interacted with heterogenous nuclear RNP (hnRNP) A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated Bcl-x(s) splicing. Our results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptotic in live cells.


2020 ◽  
Vol 48 (W1) ◽  
pp. W300-W306 ◽  
Author(s):  
Jae Y Hwang ◽  
Sungbo Jung ◽  
Tae L Kook ◽  
Eric C Rouchka ◽  
Jinwoong Bok ◽  
...  

Abstract The rMAPS2 (RNA Map Analysis and Plotting Server 2) web server, freely available at http://rmaps.cecsresearch.org/, has provided the high-throughput sequencing data research community with curated tools for the identification of RNA binding protein sites. rMAPS2 analyzes differential alternative splicing or CLIP peak data obtained from high-throughput sequencing data analysis tools like MISO, rMATS, Piranha, PIPE-CLIP and PARalyzer, and then, graphically displays enriched RNA-binding protein target sites. The initial release of rMAPS focused only on the most common alternative splicing event, skipped exon or exon skipping. However, there was a high demand for the analysis of other major types of alternative splicing events, especially for retained intron events since this is the most common type of alternative splicing in plants, such as Arabidopsis thaliana. Here, we expanded the implementation of rMAPS2 to facilitate analyses for all five major types of alternative splicing events: skipped exon, mutually exclusive exons, alternative 5′ splice site, alternative 3′ splice site and retained intron. In addition, by employing multi-threading, rMAPS2 has vastly improved the user experience with significant reductions in running time, ∼3.5 min for the analysis of all five major alternative splicing types at once.


RNA ◽  
2002 ◽  
Vol 8 (5) ◽  
pp. 671-685 ◽  
Author(s):  
WENQING ZHANG ◽  
HAIYING LIU ◽  
KYOUNGHA HAN ◽  
PAULA J. GRABOWSKI

2018 ◽  
Vol 10 (6) ◽  
pp. 405-416 ◽  
Author(s):  
Jing Liu ◽  
Xu Kong ◽  
Mengkai Zhang ◽  
Xiao Yang ◽  
Xiuqin Xu

EMBO Reports ◽  
2014 ◽  
Vol 16 (2) ◽  
pp. 178-191 ◽  
Author(s):  
Maria L Spletter ◽  
Christiane Barz ◽  
Assa Yeroslaviz ◽  
Cornelia Schönbauer ◽  
Irene R S Ferreira ◽  
...  

Methods ◽  
2017 ◽  
Vol 118-119 ◽  
pp. 171-181 ◽  
Author(s):  
Tzu-Fang Lou ◽  
Chase A. Weidmann ◽  
Jordan Killingsworth ◽  
Traci M. Tanaka Hall ◽  
Aaron C. Goldstrohm ◽  
...  

Oncogene ◽  
2013 ◽  
Vol 33 (9) ◽  
pp. 1082-1092 ◽  
Author(s):  
C Braeutigam ◽  
L Rago ◽  
A Rolke ◽  
L Waldmeier ◽  
G Christofori ◽  
...  

2019 ◽  
Author(s):  
Ling-Yu Wang ◽  
Sheng-Jun Xiao ◽  
Hiroyuki Kunimoto ◽  
Kazuaki Tokunaga ◽  
Hirotada Kojima ◽  
...  

AbstractRBM10 is an RNA-binding protein that regulates alternative splicing (AS). This protein localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs). We investigated the biological significance of RBM10 localization to S1-1 NBs, which is poorly understood. Our analyses revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs acted synergistically and were sufficient for localization of RBM10 to S1-1 NBs. Furthermore, the C2H2 ZnF not only acted as an NBTS, but was also essential for regulation of AS by RBM10. RBM10 did not participate in S1-1 NB formation. We confirmed the previous finding that localization of RBM10 to S1-1 NBs increases as cellular transcriptional activity decreases and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in these structures via its NBTSs when cellular transcription decreases. We propose that the NB-targeting activity of the C2H2 ZnF is induced when it is not bound to pre-mRNA or the splicing machinery complex under conditions of reduced transcription.


2020 ◽  
Vol 66 (5) ◽  
pp. 459-467
Author(s):  
Manami SENOO ◽  
Hiroshi HOZOJI ◽  
Yu ISHIKAWA-YAMAUCHI ◽  
Takashi TAKIJIRI ◽  
Sho OHTA ◽  
...  

2019 ◽  
Vol 40 (4) ◽  
pp. 153-161 ◽  
Author(s):  
Yuuki HORII ◽  
Takahiko SHIINA ◽  
Saki UEHARA ◽  
Kanako NOMURA ◽  
Hiroki SHIMAOKA ◽  
...  

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