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 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.

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

Esg1, expressed exclusively in preimplantation embryos, germline, and embryonic stem cells, is a putative RNA-binding protein with broad RNA targets

2006 ◽  
Vol 48 (6) ◽  
pp. 381-390 ◽  
Author(s):  
Tetsuya S. Tanaka ◽  
Isabel Lopez de Silanes ◽  
Lioudmila V. Sharova ◽  
Hidenori Akutsu ◽  
Toshiyuki Yoshikawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Embryonic Stem ◽  
Preimplantation Embryos ◽  
Rna Targets

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

scholarly journals Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

Cell Reports ◽  
2021 ◽  
Vol 35 (9) ◽  
pp. 109198
Author(s):  
Shlomi Dvir ◽  
Amir Argoetti ◽  
Chen Lesnik ◽  
Mark Roytblat ◽  
Kohava Shriki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Embryonic Stem

scholarly journals Identification and characterization of a 44 kDa protein that binds specifically to the 3′-untranslated region of CYP2a5 mRNA: inducibility, subcellular distribution and possible role in mRNA stabilization

1996 ◽  
Vol 313 (3) ◽  
pp. 1029-1037 ◽  
Author(s):  
Olivier GENESTE ◽  
Françoise RAFFALLI ◽  
Matti A. LANG
Keyword(s):  
Half Life ◽  
Untranslated Region ◽  
Translational Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Blocking Agent ◽  
Subcellular Fractionation ◽  
Mrna Stabilization ◽  
Nuclear Extracts

Stabilization of mRNA is important in the regulation of CYP2a5 expression but the factors involved in the process are not known [Aida and Negishi (1991) Biochemistry 30, 8041–8045]. In this paper, we describe, for the first time, a protein that binds specifically to the 3′-untranslated region of CYP2a5 mRNA and which is inducible by pyrazole, a compound known to increase the half-life of CYP2a5 mRNA. We also demonstrate that pyrazole treatment causes an elongation of the CYP2a5 mRNA poly(A) tail, and that phenobarbital, which is transcriptional activator of the CYP2a5 gene that does not affect the mRNA half-life, neither induces the RNA-binding protein nor affects the poly(A) tail size. SDS/PAGE of the UV-cross-linked RNA–protein complex demonstrated that the RNA-binding protein has an apparent molecular mass of 44 kDa. The protein-binding site was localized to a 70-nucleotide region between bases 1585 and 1655. Treatment of cytoplasmic extracts with an SH-oxidizing agent, diamide, an SH-blocking agent, N-ethylmaleimide or potato acid phosphatase abolished complex-formation, suggesting that the CYP2a5 mRNA-binding protein is subject to post-translational regulation. Subcellular fractionation showed that the 44 kDa protein is present in polyribosomes and nuclei, and that its apparent induction is much stronger in polyribosomes than in nuclear extracts. We propose that this 44 kDA RNA-binding protein is involved in the stabilization of CYP2a5 mRNA by controlling the length of the poly(A) tail.

Function of RNA-binding protein Musashi-1 in stem cells

2005 ◽  
Vol 306 (2) ◽  
pp. 349-356 ◽  
Author(s):  
Hideyuki Okano ◽  
Hironori Kawahara ◽  
Masako Toriya ◽  
Keio Nakao ◽  
Shinsuke Shibata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein
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