scholarly journals Recruitment of two dyneins to an mRNA-dependent Bicaudal D transport complex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Thomas E Sladewski ◽  
Neil Billington ◽  
M Yusuf Ali ◽  
Carol S Bookwalter ◽  
Hailong Lu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Protein Complex ◽  
Binding Protein ◽  
Full Length ◽  
Mrna Transport ◽  
Binding Partners ◽  
Mrna Binding Protein ◽  
Transport Complex ◽  
Mrna Binding

We investigated the role of full-length Drosophila Bicaudal D (BicD) binding partners in dynein-dynactin activation for mRNA transport on microtubules. Full-length BicD robustly activated dynein-dynactin motility only when both the mRNA binding protein Egalitarian (Egl) and K10 mRNA cargo were present, and electron microscopy showed that both Egl and mRNA were needed to disrupt a looped, auto-inhibited BicD conformation. BicD can recruit two dimeric dyneins, resulting in faster speeds and longer runs than with one dynein. Moving complexes predominantly contained two Egl molecules and one K10 mRNA. This mRNA-bound configuration makes Egl bivalent, likely enhancing its avidity for BicD and thus its ability to disrupt BicD auto-inhibition. Consistent with this idea, artificially dimerized Egl activates dynein-dynactin-BicD in the absence of mRNA. The ability of mRNA cargo to orchestrate the activation of the mRNP (messenger ribonucleotide protein) complex is an elegant way to ensure that only cargo-bound motors are motile.

Immuno‐detection of mRNA‐binding protein complex in human cells under transmission electron microscopy

2019 ◽  
Vol 82 (6) ◽  
pp. 680-688
Author(s):  
Qingfeng Ma ◽  
Takanori Tatsuno ◽  
Yuka Nakamura ◽  
Shin‐Ichi Izumi ◽  
Naohisa Tomosugi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Protein Complex ◽  
Binding Protein ◽  
Human Cells ◽  
Transmission Electron ◽  
Mrna Binding Protein ◽  
Mrna Binding

scholarly journals Regulation of LH Receptor mRNA Binding Protein by miR-122 in Rat Ovaries

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4826-4834 ◽  
Author(s):  
Bindu Menon ◽  
Jennifer Sinden ◽  
Meghan Franzo-Romain ◽  
Raman Bhadradri Botta ◽  
K. M. J. Menon
Keyword(s):  
Nucleic Acid ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Binding Protein ◽  
Locked Nucleic Acid ◽  
Down Regulation ◽  
Lh Receptor ◽  
Mrna Binding Protein ◽  
Mrna Binding

LH receptor (LHR) expression in the ovary is regulated by the RNA binding protein, (LHR mRNA binding protein [LRBP]), which has been identified as being mevalonate kinase. This study examined the role of microRNA miR-122 in LRBP-mediated LHR mRNA expression. Real-time PCR analysis of ovaries from pregnant mare serum gonadotropin/human chorionic gonadotropin (hCG)-primed female rats treated with hCG to down-regulate LHR expression showed that an increase in miR-122 expression preceded LHR mRNA down-regulation. The expression of miR-122 and its regulation was confirmed using fluorescent in situ hybridization of the frozen ovary sections using 5′-fluorescein isothiocyanate-labeled miR-122 locked nucleic acid probe. The increased expression of miR-122 preceded increased expression of LRBP mRNA and protein, and these increases were followed by LHR mRNA down-regulation. Inhibition of protein kinase A (PKA) and ERK1/2 signaling pathways by H89 and UO126, respectively, attenuated the hCG-mediated up-regulation of miR-122 levels. This was also confirmed in vitro using human granulosa cells. These results suggest the possibility that hCG-mediated miR-122 expression is mediated by the activation of cAMP/PKA/ERK signaling pathways. Inhibition of miR-122 by injection of the locked nucleic acid-conjugated antagomir of miR-122 abrogated the hCG-mediated increases in LRBP protein expression. Because it has been previously shown that miR-122 regulates sterol regulatory element-binding proteins (SREBPs) and SREBPs, in turn, regulate LRBP expression, the role of SREBPs in miR-122-mediated increase in LRBP expression was then examined. The levels of active forms of both SREBP-1a and SREBP-2 were increased in response to hCG treatment, and the stimulatory effect was sustained up to 4 hours. Taken together, our results suggest that hCG-induced down-regulation of LHR mRNA expression is mediated by activation of cAMP/PKA/ERK pathways to increase miR-122 expression, which then increases LRBP expression through the activation of SREBPs.

scholarly journals The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer

2014 ◽  
Vol 29 ◽  
pp. 3-12 ◽  
Author(s):  
Marcell Lederer ◽  
Nadine Bley ◽  
Christian Schleifer ◽  
Stefan Hüttelmaier
Keyword(s):  
Binding Protein ◽  
Mrna Binding Protein ◽  
Mrna Binding

scholarly journals Recruitment of Two Dyneins to an mRNA-Dependent Bicaudal D Transport Complex

2018 ◽  
Author(s):  
Thomas E. Sladewski ◽  
Neil Billington ◽  
M. Yusuf Ali ◽  
Carol S. Bookwalter ◽  
Hailong Lu ◽  
...  
Keyword(s):  
Single Molecule ◽  
Optimal Transport ◽  
Adaptor Proteins ◽  
Full Length ◽  
Messenger Ribonucleoprotein ◽  
Mrna Binding Protein ◽  
Run Lengths ◽  
Transport Complex ◽  
Mrna Binding

AbstractWe investigated the role of binding partners of full-length Drosophila Bicaudal D (BicD) in the activation of dynein-dynactin motility for mRNA transport on microtubules. In single-molecule assays, full-length BicD robustly activated dynein-dynactin only when both the mRNA binding protein Egalitarian (Egl), and K10 mRNA cargo were present. Electron microscopy showed that both Egl and mRNA were needed to disrupt an auto-inhibited, looped BicD conformation that sterically prevents dynein-dynactin binding. In vitro reconstituted messenger ribonucleoprotein (mRNP) complexes with two Egl molecules showed faster speeds and longer run lengths than mRNPs with one Egl, suggesting that cargo binding enhances dynein recruitment. Labeled dynein showed that BicD can recruit two dimeric dyneins to the mRNP, resulting in faster speeds and longer run lengths than with one dynein. The fully reconstituted mRNP provides a model for understanding how adaptor proteins and cargo cooperate to confer optimal transport properties to a dynein-driven transport complex.

scholarly journals Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein.

1991 ◽  
Vol 266 (25) ◽  
pp. 16594-16598
Author(s):  
I.J. Rondon ◽  
L.A. MacMillan ◽  
B.S. Beckman ◽  
M.A. Goldberg ◽  
T. Schneider ◽  
...  
Keyword(s):  
Binding Protein ◽  
Mrna Binding Protein ◽  
Mrna Binding
Sign in / Sign up

Export Citation Format

Share Document