scholarly journals Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP

2008 ◽  
Vol 181 (4) ◽  
pp. 639-653 ◽  
Author(s):  
Hironori Kawahara ◽  
Takao Imai ◽  
Hiroaki Imataka ◽  
Masafumi Tsujimoto ◽  
Ken Matsumoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Translation Initiation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Stress Granules ◽  
Translational Repression ◽  
Rna Recognition Motifs ◽  
Recognition Motifs

Musashi1 (Msi1) is an RNA-binding protein that is highly expressed in neural stem cells. We previously reported that Msi1 contributes to the maintenance of the immature state and self-renewal activity of neural stem cells through translational repression of m-Numb. However, its translation repression mechanism has remained unclear. Here, we identify poly(A) binding protein (PABP) as an Msi1-binding protein, and find Msi1 competes with eIF4G for PABP binding. This competition inhibits translation initiation of Msi1's target mRNA. Indeed, deletion of the PABP-interacting domain in Msi1 abolishes its function. We demonstrate that Msi1 inhibits the assembly of the 80S, but not the 48S, ribosome complex. Consistent with these conclusions, Msi1 colocalizes with PABP and is recruited into stress granules, which contain the stalled preinitiation complex. However, Msi1 with mutations in two RNA recognition motifs fails to accumulate into stress granules. These results provide insight into the mechanism by which sequence-specific translational repression occurs in stem cells through the control of translation initiation.

Structural properties and RNA-binding activities of two RNA recognition motifs of a mouse neural RNA-binding protein, mouse-Musashi-1

Gene ◽  
1997 ◽  
Vol 186 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Yasuyuki Kurihara ◽  
Takashi Nagata ◽  
Takao Imai ◽  
Ado Hiwatashi ◽  
Masataka Horiuchi ◽  
...  
Keyword(s):  
Structural Properties ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Rna Recognition ◽  
Rna Recognition Motifs ◽  
Recognition Motifs

scholarly journals RNA-binding protein Maca is crucial for gigantic male fertility factor gene expression, spermatogenesis, and male fertility, in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009655
Author(s):  
Li Zhu ◽  
Ryuya Fukunaga
Keyword(s):  
Gene Expression ◽  
Male Fertility ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Large Male ◽  
Rna Recognition Motifs ◽  
Fertility Factor ◽  
Recognition Motifs ◽  
Successful Expression

During spermatogenesis, the process in which sperm for fertilization are produced from germline cells, gene expression is spatiotemporally highly regulated. In Drosophila, successful expression of extremely large male fertility factor genes on Y-chromosome spanning some megabases due to their gigantic intron sizes is crucial for spermatogenesis. Expression of such extremely large genes must be challenging, but the molecular mechanism that allows it remains unknown. Here we report that a novel RNA-binding protein Maca, which contains two RNA-recognition motifs, is crucial for this process. maca null mutant male flies exhibited a failure in the spermatid individualization process during spermatogenesis, lacked mature sperm, and were completely sterile, while maca mutant female flies were fully fertile. Proteomics and transcriptome analyses revealed that both protein and mRNA abundance of the gigantic male fertility factor genes kl-2, kl-3, and kl-5 (kl genes) are significantly decreased, where the decreases of kl-2 are particularly dramatic, in maca mutant testes. Splicing of the kl-3 transcripts was also dysregulated in maca mutant testes. All these physiological and molecular phenotypes were rescued by a maca transgene in the maca mutant background. Furthermore, we found that in the control genetic background, Maca is exclusively expressed in spermatocytes in testes and enriched at Y-loop A/C in the nucleus, where the kl-5 primary transcripts are localized. Our data suggest that Maca increases transcription processivity, promotes successful splicing of gigantic introns, and/or protects transcripts from premature degradation, of the kl genes. Our study identified a novel RNA-binding protein Maca that is crucial for successful expression of the gigantic male fertility factor genes, spermatogenesis, and male fertility.

Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein

2010 ◽  
Vol 1358 ◽  
pp. 20-29 ◽  
Author(s):  
Kosuke Saito ◽  
Noboru Fukuda ◽  
Taro Matsumoto ◽  
Yuji Iribe ◽  
Akiko Tsunemi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Low Temperature ◽  
Neural Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling

2017 ◽  
Vol 31 (18) ◽  
pp. 1910-1925 ◽  
Author(s):  
Yoshika Hayakawa-Yano ◽  
Satoshi Suyama ◽  
Masahiro Nogami ◽  
Masato Yugami ◽  
Ikuko Koya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Neural Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mrna Processing

scholarly journals The RNA-binding protein Orb2 is associated with microcephaly and supports centrosome asymmetry in neural stem cells

2021 ◽  
Author(s):  
Beverly V. Robinson ◽  
Junnan Fang ◽  
Dipen S. Mehta ◽  
Joseph Buehler ◽  
Dorothy Lerit
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Translational Regulation ◽  
Rna Binding ◽  
Asymmetric Cell Division ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Composition ◽  
Rna Targets ◽  
Stem Cell Pool

To maintain a balance of self-renewal versus neurogenesis, neural stem cells (NSCs) undergo repeated cycles of asymmetric cell division along an invariant polarity axis instructed by centrosomes. During interphase, the NSC centrosomes are defined by marked asymmetries in protein composition and functional activity as microtubule-organizing centers. Here, we show a conserved RNA-binding protein, Orb2, supports centrosome asymmetry in interphase NSCs. While Orb2 localizes to the active apical centrosome, it promotes the transient inactivation of the basal centrosome required for centrosome segregation and spindle morphogenesis. Orb2 is required cell autonomously within NSCs to support centrosome asymmetry and maintenance of the stem cell pool. Conversely, loss of orb2 manifests in microcephaly independent of Orb2 function in NSCs. We suggest Orb2 plays opposing roles in centrosome activation and inactivation, possibly through the translational regulation of multiple mRNA substrates. Bioinformatics uncovers a significant overlap among RNA targets between Drosophila Orb2 and human CPEB4, consistent with a conserved role for CPEB proteins in in centrosome regulation and neurodevelopment.

scholarly journals Involvement of Cold Inducible RNA-Binding Protein in Severe Hypoxia-Induced Growth Arrest of Neural Stem Cells In Vitro

2016 ◽  
Vol 54 (3) ◽  
pp. 2143-2153 ◽  
Author(s):  
Qian Zhang ◽  
Ya-Zhou Wang ◽  
Wenbin Zhang ◽  
Xiaoming Chen ◽  
Jiye Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Growth Arrest ◽  
Severe Hypoxia
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