Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype.

Kislauskis, Edward H.; Zhu, Xiaochun; Singer, Robert H.

doi:10.1083/jcb.127.2.441

Cited by 476 publications

(433 citation statements)

References 53 publications

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“…The idea of a functional correlate for 3h-UTR-directed localization of the AT "A mRNA is interesting given the recent identification of mRNA localization motifs (zipcodes) in the 3h-UTR of the β-actin mRNA [44]. These evolutionarily conserved zipcodes are sequences of approx.…”

Section: Discussionmentioning

confidence: 99%

“…These zipcodes are responsible for the specific localization of β-actin mRNA and, by analogy, any mRNA containing these codes. Removal of the β-actin zipcode resulted in disordering of the actin filaments, loss of cell structure and alteration of normal cell function [44]. Sequence analysis revealed the presence of such a zipcode in the rat AT "A 3h-UTR ( Figure 9).…”

Section: Discussionmentioning

confidence: 99%

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Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

Thekkumkara

Gruber

Motel

et al. 1998

Biochemical Journal

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We demonstrate a functional role for the 3ʹ-untranslated region (3ʹ-UTR) of the angiotensin II (Ang II) receptor subtype AT1A mRNA in Chinese hamster ovary (CHO-K1) cells by stably transfecting the coding region of the receptor gene with or without the 845 bp 3ʹ-UTR. Two cell lines expressing similar levels of cell-surface receptors (with 3ʹ-UTR, Bmax = 571 fmol/mg protein; without 3ʹ-UTR, Bmax = 663 fmol/mg protein) were used in the present study. Both cell lines expressed high-affinity receptors (with 3ʹ-UTR, Kd = 0.83 nM; without 3ʹ-UTR, Kd = 0.82 nM), and binding studies with 125I-labelled Ang II in the presence of GTP[S] demonstrated that both coupled to heterotrimeric G-proteins. Despite these similarities, significant differences were observed for receptor-mediated cell signalling pathways. In cells without the 3ʹ-UTR, Ang II stimulated an increase in cAMP accumulation (11-fold above control) and in cells with the 3ʹ-UTR no stimulation was observed, which was consistent with previous observations in most endogenous Ang II receptor (AT1)-expressing cells. Activation of cAMP by Ang II in cells without the 3ʹ-UTR correlated with an inhibition of DNA synthesis, determined by [3H]thymidine incorporation. Ang II-mediated responses were blocked by EXP3174, a selective non-peptide receptor antagonist. We also observed differences in the transient profiles of intracellular calcium between cells with and without the 3ʹ-UTR in response to Ang II. In cells with the 3ʹ-UTR, a sustained level of intracellular calcium was observed after Ang II stimulation, whereas cells without the 3ʹ-UTR displayed a full return to basal level within 50 s of Ang II treatment. Even though the expressed exogenous gene is under the control of a constitutively expressing promoter (cytomegalovirus promoter), Northern-blot analysis revealed a considerably greater accumulation of AT1A mRNA in cells without the 3ʹ-UTR compared with cells with the 3ʹ-UTR. Analysis of the decay rate of the AT1A mRNA in cells with and without the 3ʹ-UTR revealed that the normally unstable AT1A receptor mRNA became highly stable by removing its 3ʹ-UTR, identifying a role for the 3ʹ-UTR in mRNA destabilization. Interestingly, both cells express similar levels of receptors at the cell surface, suggesting that the 3ʹ-UTR is also involved in the efficient translation and/or translocation of the receptor protein to the plasma membrane. We hypothesized that these 3ʹ-UTR-mediated functions of the receptor are regulated by RNA-binding proteins. To identify possible RNA-binding proteins for the AT1A 3ʹ-UTR, cellular extracts were prepared from parental CHO-K1 cells and 3ʹ-UTR-binding assays, electrophoretic mobility-shift assays and UV crosslinking studies were performed. A major cellular protein of 55 kDa was identified, which specifically interacted with the 3ʹ-UTR. Our data suggest that the 3ʹ-UTR of the AT1A can control specific receptor functions, perhaps via selective recognition of the 3ʹ-UTR by RNA-binding proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

Thekkumkara

Gruber

Motel

et al. 1998

Biochemical Journal

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“…Third, axoplasmic synthesis of cytoskeletal proteins such as NF-M could play an important role in the construction and maintenance of the highly polar neuronal cytoskeleton. For example, the prevention of β-actin mRNA localization to the cell periphery of chicken embryonic fibroblasts results in the disorganization of the actin cytoskeleton, suggesting that the maintenance of cell polarity requires localized protein synthesis of this cytoskeletal element [11].…”

mentioning

confidence: 99%

Medium weight neurofilament mRNA in goldfish Mauthner axoplasm

Weiner

Zorn

Krieg

et al. 1996

Neuroscience Letters

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Although axons are generally considered to lack the ability to synthesize proteins, the Mauthner axon (M-axon) of the goldfish has been reported to contain some of the basic components of the translational machinery, such as transfer RNA (tRNA), ribosomal RNA (rRNA), and ribosomes. To determine if the M-axon also contains mRNA, we isolated samples of M-axoplasm free of glial contamination as demonstrated by the absence of glial-specific mRNA and protein. KeywordsAxoplasmic protein synthesis; Goldfish Mauthner axon; mRNA; Neurofilament protein The nerve axon is generally considered to depend entirely on its cell body for trophic support such as synthesis of proteins necessary to maintain axonal structure and function. This assumption is supported by data showing that a distal axonal segment severed from its cell body in mammals typically degenerates within hours to days [10]. However, when axons are severed from their cell bodies in invertebrates [2] or lower vertebrates such as the goldfish [18], the distal axonal segment often survives for months to years. Proteins in an axon isolated from its cell body could be maintained only through some combination of (1) Although often regarded as a particularly unlikely mechanism to maintain axonai proteins [2,16], axoplasmic protein synthesis has been reported for squid giant axons [7] and goldfish Mauthner axons (M-axons) [14]. The M-axon is a particularly advantageous preparation because more basic components of the translational machinery (transfer RNA (tRNA), ribosomal RNA (rRNA), and ribosomes) have been identified in the M-axon [13][14][15] compared to any other vertebrate axon. However, no direct evidence has been published for any mRNAs that could function as templates for protein synthesis in M-axoplasm, although mRNAs have been reported in other vertebrate axons [9,19] for which the presence of translational machinery

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“…Il est possible de bloquer la localisation de l'ARNm de l'actine β dans des cellules vivantes grâce à des oligonucléotides antisens qui peuvent s'apparier in vivo à la séquence de localisation de l'ARN et empêcher sa fonction. Ainsi, il a été démontré que l'inhibition de la localisation de l'ARNm de l'actine β entraîne une désorga-nisation du cytosquelette d'actine dans les fibroblastes, ainsi que l'incapacité de la cellule à se mouvoir continûment dans une même direction [5][6][7]. Ce phénomène intervient sans que la quantité totale d'actine β soit modifée, indiquant que la localisation de l'ARNm participe à la polarisation du cytosquelette.…”

Section: Localisation Des Arnm De L'actine Et Polarisation De La Mobiunclassified

Polarité cellulaire et localisation intracellulaire des ARNm de l’actine

Lavoie

Basyuk²,

Bordonne³

et al. 2004

Med Sci (Paris)

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Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype.

Cited by 476 publications

References 53 publications

Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

Functional role for the angiotensin II receptor (AT1A) 3′-untranslated region in determining cellular responses to agonist: evidence for recognition by RNA binding proteins

Medium weight neurofilament mRNA in goldfish Mauthner axoplasm

Polarité cellulaire et localisation intracellulaire des ARNm de l’actine

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