Structural requirements of (2′–5′) oligoadenylate for protein synthesis inhibition in human fibroblasts

Drocourt, Jean-Louis; Dieffenbach, Carl W.; Ts’o, Paul O. P.; Justesen, Just; Thang, M.N.

doi:10.1093/nar/10.6.2163

Cited by 37 publications

(13 citation statements)

References 33 publications

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“…Control cultures were treated with calcium phosphate, but without oligonucleotides and the incorporation of [35S]methionine into control cultures was taken as 100%. shown), in agreement with [9] on HF926 cells. (2' -5 ')p33 'dA4 either enzymatically or chemically synthesized is as good as or a better inhibitor of protein synthesis than is (2' -5 ')p& in lysates from rabbit reticulocytes [7].…”

Section: Cellsupporting

confidence: 86%

“…The continued action of the endonuclease and the prolonged maintenance of protein synthesis inhibition may require a constant presence of (2' -5 ')psA. [9]. Thus, an analog of (2' -5 ')psA.…”

Section: The Prolonged Inhibition Of Protein Synthesismentioning

confidence: 99%

“…Since our original report on the enzymatic synthesis, increased metabolic stability and inhibition of protein synthesis by the cordycepin analog of (2' -5 ')psA, [14], studies have expanded in which modification of the 2' -terminus of the (2 ' -5 ')p3A, molecule results in (2 ' -5 ')p3An analogs which also have increased metabolic stabilities, inhibit protein synthesis and inhibit methylation of the S'cap of mRNA [9,11,13,. The eventual goal of these studies would be the design of an analog of the (2'-5')p3A, molecule that could replace the metabolically unstable (2 ' -5 ' )prA,, and be suitable for use in the treatment of virus diseases or cancer.…”

Section: The Prolonged Inhibition Of Protein Synthesismentioning

confidence: 99%

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Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)_nA, (2′–5′)ppp(3′dAp)_n3′ dA, in intact mammalian cells

Lee¹,

Suhadolnik²

1983

FEBS Letters

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The introduction of the cordycepin analog of (2′–5′)A n , (2′–5′)ppp(3′ dAp) n 3′ dA [referred to as (2′–5′)p33′ dA n ], into mouse L929 cells and cultured human fibroblasts resulted in a dose‐dependent inhibition of protein synthesis which was comparable to the inhibition observed by (2′–5′)ppp(Ap) n A [referred to as (2′–5′)p3A n ]. The inhibition of protein synthesis by (2′–5′)p33′ dA n was much more persistent than that of the naturally occurring (2′–5′)p3A n following prolonged incubation of cells. Furthermore, the (2′–5′)p3A n was cytotoxic to mammalian cells in culture, whereas the (2′–5′)p33′dA n was not.

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Section: Cellsupporting

confidence: 86%

Section: The Prolonged Inhibition Of Protein Synthesismentioning

confidence: 99%

Section: The Prolonged Inhibition Of Protein Synthesismentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)_nA, (2′–5′)ppp(3′dAp)_n3′ dA, in intact mammalian cells

Lee¹,

Suhadolnik²

1983

FEBS Letters

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“…As regard the role of the adenine rings in 2‐5A, it has been reported that RNase L has drastically lower affinity for cytidine, uridine, or inosine analogs, [10] in Figure 5D, compared to its adenine counterpart [6] (Torrence et al , 1984). Similarly, [11] failed to activate RNase L (Drocourt et al , 1982). Torrence et al (1984) suggested that RNase L interacts with N1 and/or N6 of the adenine ring of 2‐5A.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for recognition of 2′,5′-linked oligoadenylates by human ribonuclease L

Tanaka

Nakanishi

Kusakabe

et al. 2004

EMBO J

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An interferon-induced endoribonuclease, ribonuclease L (RNase L), is implicated in both the molecular mechanism of action of interferon and the fundamental control of RNA stability in mammalian cells. RNase L is catalytically active only after binding to an unusual activator molecule containing a 5 0 -phosphorylated 2 0 ,5 0 -linked oligoadenylate (2-5A), in the N-terminal half. Here, we report the crystal structure of the N-terminal ankyrin repeat domain (ANK) of human RNase L complexed with the activator 2-5A. This is the first structural view of an ankyrin repeat structure directly interacting with a nucleic acid, rather than with a protein. The ANK domain folds into eight ankyrin repeat elements and forms an extended curved structure with a concave surface. The 2-5A molecule is accommodated at a concave site and directly interacts with ankyrin repeats 2-4. Interestingly, two structurally equivalent 2-5A binding motifs are found at repeats 2 and 4. The structural basis for 2-5A recognition by ANK is essential for designing stable 2-5As with a high likelihood of activating RNase L.

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“…Furthermore, the biological role of 2′,5′-linked heteronucleotides, which might be synthesized in cells, is not known [1,15,20,21]. …”

Section: Introductionmentioning

confidence: 99%

Natural Occurrence of 2′,5′-Linked Heteronucleotides in Marine Sponges

et al. 2010

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2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′ p5′U, A2′p5′C, G2′p5′A and G2′ p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family.

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Structural requirements of (2′–5′) oligoadenylate for protein synthesis inhibition in human fibroblasts

Cited by 37 publications

References 33 publications

Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)_nA, (2′–5′)ppp(3′dAp)_n3′ dA, in intact mammalian cells

Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)_nA, (2′–5′)ppp(3′dAp)_n3′ dA, in intact mammalian cells

Structural basis for recognition of 2′,5′-linked oligoadenylates by human ribonuclease L

Natural Occurrence of 2′,5′-Linked Heteronucleotides in Marine Sponges

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Structural requirements of (2′–5′) oligoadenylate for protein synthesis inhibition in human fibroblasts

Cited by 37 publications

References 33 publications

Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)nA, (2′–5′)ppp(3′dAp)n3′ dA, in intact mammalian cells

Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)nA, (2′–5′)ppp(3′dAp)n3′ dA, in intact mammalian cells

Structural basis for recognition of 2′,5′-linked oligoadenylates by human ribonuclease L

Natural Occurrence of 2′,5′-Linked Heteronucleotides in Marine Sponges

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Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)_nA, (2′–5′)ppp(3′dAp)_n3′ dA, in intact mammalian cells

Inhibition of protein synthesis by the cordycepin analog of (2′–5′)ppp(Ap)_nA, (2′–5′)ppp(3′dAp)_n3′ dA, in intact mammalian cells