cis-Acting signals and trans-acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells

1995 ◽  
Vol 13 (2) ◽  
pp. 113-127 ◽  
Author(s):  
L. Behar ◽  
R. Marx ◽  
E. Sadot ◽  
J. Barg ◽  
I. Ginzburg
2021 ◽  
Author(s):  
Cristina Tocchini ◽  
Michele Rohner ◽  
Stephen E. Von Stetina ◽  
Susan E. Mango

mRNA localization is an evolutionarily widespread phenomenon that facilitates sub-cellular protein targeting. Extensive work has focused on mRNA targeting through “zip codes” within untranslated regions (UTRs), while much less is known about translation-dependent cues. Here, we examine mRNA localization in Caenorhabditis elegans embryonic epithelia. From an smFISH-based survey, we identified mRNAs associated with the cell membrane or cortex, and with apical junctions in a stage- and cell type-specific manner. Mutational analyses for one of these transcripts, dlg-1/discs large, revealed that it relied on a translation-dependent process and did not require its 5′ or 3′ UTR. We suggest a model in which dlg-1 transcripts are co-translationally colocalized with the encoded protein: first the translating complex goes to the cell membrane through sequences of the SH3 domain, and then to the apical junction by the L27 and PDZ sequences. In addition, the Hook and GuK sequences contribute to the second step: they are required for mRNA, but not protein, to accumulate at the apical junctions from locations at or near the membrane. These studies identify a translation-based process for mRNA localization within developing epithelia and determine the necessary cis-acting sequences for dlg-1 mRNA targeting.


2004 ◽  
Vol 32 (5) ◽  
pp. 702-704 ◽  
Author(s):  
H. Chabanon ◽  
D. Nury ◽  
I. Mickleburgh ◽  
B. Burtle ◽  
J. Hesketh

Subcellular localization of mRNAs is a key mechanism for the synthesis of proteins close to their site of function. The mRNA encoding MT-1 (metallothionein-1) is localized in the perinuclear cytoplasm, where it is associated with cytoskeletal-bound polysomes. This localization relies on sequences present in the 3′-UTR (3′-untranslated region). The present study aims to characterize the cis-acting localization element(s) within the 3′-UTR. Using transfected cells expressing tagged MT-1 differing in their 3′-UTRs (deleted or mutated), the section(s) of this region required for directing MT-1 transcripts to the perinuclear cytoplasm has been investigated. Different 3′-UTRs were also used in UV cross-linking experiments that highlighted two distinct regions (nt 26–30 and 66–76) necessary for the binding of a protein of approx. 50 kDa, presumably involved in the mRNA targeting. The poor sequence homology between the MT-1 3′-UTR of various species, together with the bipartite nature of the required cis-element, indicates the involvement of a particular structure in the localization signal. The secondary structure of the MT-1 3′-UTR was investigated using enzymic and chemical probing. Current structural analysis of mutant 3′-UTRs will allow the critical structural features of the MT-1 mRNA perinuclear localization signal to be defined.


Development ◽  
2021 ◽  
Author(s):  
Cristina Tocchini ◽  
Michèle Rohner ◽  
Laurent Guerard ◽  
Poulomi Ray ◽  
Stephen E. Von Stetina ◽  
...  

mRNA localization is an evolutionarily widespread phenomenon that can facilitate subcellular protein targeting. Extensive work has focused on mRNA targeting through “zip-codes” within untranslated regions (UTRs), while much less is known about translation-dependent cues. Here, we examine mRNA localization in Caenorhabditis elegans embryonic epithelia. From an smFISH-based survey, we identified mRNAs associated with the cell membrane or cortex, and with apical junctions in a stage- and cell type-specific manner. Mutational analyses for one of these transcripts, dlg-1/discs large, revealed that it relied on a translation-dependent process and did not require its 5’ or 3'UTRs. We suggest a model in which dlg-1 transcripts are co-translationally localized with the nascent protein: first the translating complex goes to the cell membrane using sequences located at the carboxy-terminus/3’ end, and then apically using amino-terminal/5’ sequences. These studies identify a translation-based process for mRNA localization within developing epithelia and determine the necessary cis-acting sequences for dlg-1 mRNA targeting.


2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.


2011 ◽  
Vol 8 (2) ◽  
pp. 33
Author(s):  
Norfaezah Mazalan ◽  
Mazatulikhma Mat Zain ◽  
Nor Saliyana Jumali ◽  
Norhanim Mohalid ◽  
Zurina Shaameri ◽  
...  

Recently, research and development in the field of drug delivery systems (DDS) facilitating site-specific therapy has reached significant progression. DDS based on polymer micelles, coated micro- and nanoparticles, and various prodrug systems including water-soluble polymer have been prepared and extensively studied as novel drugs designed for cancer chemotherapy and brain delivery. Since polymers are going to be used in human, this study has the interest of testing two types of polymer, polyimides (PI) and polyphenylenevinylene (PPV) on neuronal cells. The objective of this study was to determine the possible neurotoxicity and potential neuroprotective effects of PI and PPV towards SH-SY5Y neuronal cells challenged by hydrogen peroxide (H2O2) as an oxidant. Cells were pretreated with either PI or PPV for 1 hour followed by incubation for 24 hour with 100 µM of H2O2. MTS assay was used to assess cell viability. Results show that PI and PPV are not harmful within the concentration up to 10 µM and 100 µM, respectively. However, PI and PPV do not protect neuronal cells against toxicity induced by H2O2 or further up the cell death.


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