The Cap Structure of Eukaryotic Messenger RNA and its Interaction with Cap-binding Protein

Rhoads, Robert E.

doi:10.1007/978-3-642-70203-7_3

Cited by 29 publications

(7 citation statements)

References 101 publications

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“…First, translation observed in vitro has both cap-dependent and cap-independent components, and the distribution between the two can be influenced by a variety of factors (salt concentration, pH, mRNA concentration, the particular lysate used, etc. ; for review, see Rhoads 1985). The amount of cap-independent translation can be determined with a control mRNA capped with Gp 3 G, which is not recognized by eIF4E.…”

Section: Translational Efficiency Of Mrnas Capped With Novel Arcasmentioning

confidence: 99%

Novel “anti-reverse” cap analogs with superior translational properties

Jemielity

Fowler²,

Zuberek³

et al. 2003

RNA

238

275

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Section: Translational Efficiency Of Mrnas Capped With Novel Arcasmentioning

confidence: 99%

Novel “anti-reverse” cap analogs with superior translational properties

Jemielity

Fowler²,

Zuberek³

et al. 2003

RNA

238

275

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“…1) composed of a 7-methylguanosine connected with the first transcribed nucleotide (N) via a 5 ′ ,5 ′ -triphosphate bridge (Furuichi and Shatkin 2000). The cap plays a crucial role in several cellular processes, such as pre-mRNA splicing (Sharp 1994), transport of RNA from the nucleus to the cytoplasm (Lewis and Izaurralde 1997), protection of mRNA against degradation (Rhoads 1985), and translation initiation (Gingras et al 1999). Over the years, chemically modified cap analogs have been used for biochemical, biophysical, and structural studies on mechanisms of the aforementioned processes (Niedzwiecka et al 2002;Grudzien et al 2004;Jankowska-Anyszka et al 2011;Ziemniak et al 2013).…”

Section: All Cellular Eukaryotic Mrnas Have At Theirmentioning

confidence: 99%

Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors

Piecyk

Łukaszewicz

Darżynkiewicz

et al. 2014

RNA

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Synthetic analogs of the 5′ end of mRNA (cap structure) are widely used in molecular studies on mechanisms of cellular processes such as translation, intracellular transport, splicing, and turnover. The best-characterized cap binding protein is translation initiation factor 4E (eIF4E). Recognition of the mRNA cap by eIF4E is a critical, rate-limiting step for efficient translation initiation and is considered a major target for anticancer therapy. Here, we report a facile methodology for the preparation of N2-triazole-containing monophosphate cap analogs and present their biological evaluation as inhibitors of protein synthesis. Five analogs possessing this unique hetero-cyclic ring spaced from the m7-guanine of the cap structure at a distance of one or three carbon atoms and/or additionally substituted by various groups containing the benzene ring were synthesized. All obtained compounds turned out to be effective translation inhibitors with IC 50 similar to dinucleotide triphosphate m 7 GpppG. As these compounds possess a reduced number of phosphate groups and, thereby, a negative charge, which may support their cell penetration, this type of cap analog might be promising in terms of designing new potential therapeutic molecules. In addition, an exemplary dinucleotide from a corresponding mononucleotide containing benzyl substituted 1,2,3-triazole was prepared and examined. The superior inhibitory properties of this analog (10-fold vs. m 7 GpppG) suggest the usefulness of such compounds for the preparation of mRNA transcripts with high translational activity.

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“…The presence and effects of such interactions have been presumed in the interpretation of many biological functions of the 7-methylguanosine, other alkylated nucleic acid bases and their nucleotide derivatives. One example is the eukaryotic mRNA with a special CAP structure (see [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] and the references therein) (the 5'cap is found on the end of mRNA molecule and consists of a guanine nucleotide connected to the mRNA via an unusual 5' to 5' triphosphate linkage). This guanosine is methylated on the 7 position directly after capping in vitro by a methyl transferase.…”

Section: Introductionmentioning

confidence: 99%

Estimation of stacking interaction of 7-methyl-guanosine

Labádi¹

2008

Arkivoc

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A new technique with which to estimate the affinity of any organic compound for participation in stacking interactions was applied to 7-methylguanosine. A microcalorimetric method was used. The compositions and apparent stability constants of the associations formed between caffeine and indole, 7-methylguanosine and indole, and caffeine and 7-methylguanosine were determined. It was concluded that, in respect of stacking affinity, 7-methylguanosine in protonated form behaves similarly to caffeine.

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The Cap Structure of Eukaryotic Messenger RNA and its Interaction with Cap-binding Protein

Cited by 29 publications

References 101 publications

Novel “anti-reverse” cap analogs with superior translational properties

Novel “anti-reverse” cap analogs with superior translational properties

Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors

Estimation of stacking interaction of 7-methyl-guanosine

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