Existence of methylated messenger RNA in mouse L cells

Perry, Robert P.; Kelley, Dawn E.

doi:10.1016/0092-8674(74)90153-6

Cited by 399 publications

(391 citation statements)

References 21 publications

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“…Since SAM has functions other than polyamine synthesis, including methylation reactions involving DNA (35). RNA (43). phospholipids, and other macromolecules (44), it is possible that MTX might also affect these functions in relation to cell proliferation and protein (including Ig) synthesis.…”

Section: Discussionmentioning

confidence: 99%

The in vitro effects of methotrexate on peripheral blood mononuclear cells: Modulation by methyl donors and spermidine

Nesher

Moore

1990

Arthritis & Rheumatism

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The mode of action of low-dose methotrexate (MTX) in rheumatoid arthritis (RA) is unclear. The effects of MTX are mediated primarily through inhibition of dihydrofolate reductase, resulting in a dosedependent inhibition of purine and pyrimidine synthesis. Other folate-dependent metabolic pathways might be secondarily affected. One such pathway is the regeneration of methionine from homocysteine, with subsequent formation of the methyl donor S-adenosylmethionine (SAM) and polyamines, which are important in cell-mediated immune reactions. To assess whether MTX inhibits S A M and polyamine synthesis in lymphocytes, pokeweed mitogerr-stimulated mononuclear cells from healthy donors were incubated with MTX. This resulted in decreased proliferation and IgG, IgM, and IgM rheumatoid factor synthesis. However, addition of folinic acid, methionine, SAM, or spermidine resulted in reversal of the MTX-mediated inhibition. These data suggest that MTX inhibits the folate-dependent pathway of methionine regeneration, thereby inhibiting S A M and polyamine synthesis. Since RA lymphocytes have in-

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Section: Discussionmentioning

confidence: 99%

The in vitro effects of methotrexate on peripheral blood mononuclear cells: Modulation by methyl donors and spermidine

Nesher

Moore

1990

Arthritis & Rheumatism

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“…[1][2][3] These studies revealed the presence of internal m 6 A, m 5 C, and ribose 2 0 OMe (Fig. 1).…”

Section: Mrnamentioning

confidence: 99%

“…Initial studies were largely limited to more abundant modifications: N 1 -methyladenosine (m 1 A), pseudouridine (C), and 2 0 -O-methylation (2 0 OMe) in tRNA and rRNA, and N 6 -methyladenosine (m 6 A), 5-methylcytidine (m 5 C), and 2 0 O methylation (2 0 OMe) in mRNA and viral RNA. [1][2][3] This early research not only began the work of exhaustively cataloging these modifications, but also began to uncover the mechanisms by which these small chemical additions influence RNA folding and function. This field has experienced a recent resurgence, particularly with respect to mRNA modifications, driven in part by technological advances in high throughput sequencing and mass spectrometry that have allowed deeper analysis of less prevalent modifications on less abundant RNA species.…”

Section: Introductionmentioning

confidence: 99%

Publisher's Note

2017

RNA Biology

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RNA modifications have long been known to be central in the proper function of tRNA and rRNA. While chemical modifications in mRNA were discovered decades ago, their function has remained largely mysterious until recently. Using enrichment strategies coupled to next generation sequencing, multiple modifications have now been mapped on a transcriptome-wide scale in a variety of contexts. We now know that RNA modifications influence cell biology by many different mechanisms -by influencing RNA structure, by tuning interactions within the ribosome, and by recruiting specific binding proteins that intersect with other signaling pathways. They are also dynamic, changing in distribution or level in response to stresses such as heat shock and nutrient deprivation. Here, we provide an overview of recent themes that have emerged from the substantial progress that has been made in our understanding of chemical modifications across many major RNA classes in eukaryotes.

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“…In eucaryotic organisms methylated nucleotides have been found in tRNA [1], rRNA [2], LnRNA [3], and mRNA [4]. Judging from the sequenced parts of tRNA [5] and rRNA [6;7], the attachment of methyl groups to RNA is a very specific process tRNA methylases retain their specificity when tested in vitro: no RNA except for heterologous tRNA is accepted and methylation takes place at positions where tRNA precursors are methylated in vivo.…”

Section: Introductionmentioning

confidence: 99%