Sequence specificity of mRNA N6-adenosine methyltransferase

Csépány, Tünde; Lin, Alison; Baldick, Carl J.; Beemon, Karen

doi:10.1016/s0021-9258(17)30477-5

Cited by 171 publications

(188 citation statements)

References 33 publications

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“…Surprisingly, GFP protein was detected for all of the transfected constructs, independently of whether they contained an IRES element or not. Yang et al (2017) hypothesized that this is caused by the m 6 A motif RRACH (R = G or A; H = A, C, or U) (Csepany et al 1990;Harper et al 1990), which had by chance been included in all the plasmids. Mutations of the correspond-ing motifs reduced levels of GFP.…”

Section: Translation Of Circrnasmentioning

confidence: 99%

Roles of Long Noncoding RNAs and Circular RNAs in Translation

Chekulaeva

Rajewsky

2018

Cold Spring Harb Perspect Biol

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Most of the eukaryotic genome is pervasively transcribed, yielding hundreds to thousands of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), some of which are well conserved during evolution. Functions have been described for a few lncRNAs and circRNAs but remain elusive for most. Both classes of RNAs play regulatory roles in translation by interacting with messenger RNAs (mRNAs), microRNAs (miRNAs), or mRNA-binding proteins (RBPs), thereby modulating translation in Moreover, although initially defined as noncoding, a number of lncRNAs and circRNAs have recently been reported to contain functional open reading frames (ORFs). Here, we review current understanding of the roles played by lncRNAs and circRNAs in protein synthesis and discuss challenges and open questions in the field.

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Section: Translation Of Circrnasmentioning

confidence: 99%

Roles of Long Noncoding RNAs and Circular RNAs in Translation

Chekulaeva

Rajewsky

2018

Cold Spring Harb Perspect Biol

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“…N6-methyladenosine (m 6 A) is the most abundant RNA modification ( Csepany et al, 1990 ) that stabilizes mRNAs and also modulates their localization, transport, and post-translational regulation ( Lence et al, 2019 ). The methylation of adenosine is mediated by the methyltransferase(also known as “writers”) complex consisting of METTL3, METTL14, WTAP, KIAA1429, and RBM15/RBM15B.…”

Section: Introductionmentioning

confidence: 99%

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

Qiu

Zhou

et al. 2021

Front. Cell Dev. Biol.

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The N6-methyladenosine (m6A) RNA modification regulates the expression of genes associated with various biological and pathological processes, including spontaneous abortion (SA). The aim of this study was to determine the role of the m6A demethylase fat mass and obesity (FTO)- associated protein in SA. The FTO,IGF2BP1 and IGF2BP2 mRNA levels were significantly lower in the chorionic villi obtained from spontaneously aborted pregnancies compared to that of normal pregnancies, while the expression levels of METTL3 and WTAP were significantly elevated. However, ALKBH5, YTHDF2, and IGF2BP3 were elevated with no statistical significance between groups. In addition, MDA was elevated and SOD levels were decreased in the villi tissues of the SA group compared to the normal group, which was indicative of placental oxidative stress in the former. Furthermore, the expression of FTO and HLA-G were significantly decreased in the trophoblasts of the SA patients compared to that of normal pregnant women, while that of m6A was markedly higher in the former. In addition, the HLA-G and VEGFR mRNA levels were downregulated in the SA versus the control group, and that of MMP2, MMP7, MMP9 and VEGFA were upregulated. Finally, The RIP assay showed significantly decreased levels of FTO-bound HLA-G, VEGFR and MMP9 RNA in SA patients (P < 0.05), which corresponded to an increase in transcripts enriched with the m6A antibody (P < 0.05). However, compared with normal pregnant women, the levels of HLA-G, VEGFA, VEGFR, and MMP2 mRNA bound by YTHDF2 were significantly decreased in SA patients. Compared to the normal pregnant women, both FTO- and m6A-bound MMP7 were significantly increased in SA patients (P < 0.05), but YTHDF2 almost unbound to MMP7 mRNA. In summary, the downregulation of FTO in the chorionic villi disrupts immune tolerance and angiogenesis at the maternal-fetal interface, resulting in aberrant methylation and oxidative stress that eventually leads to SA.

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“…The majority of m 6 A marks in mRNA and lncRNA are installed by a multiprotein writer complex comprising methyltransferase-like 3 (METTL3)/METTL14 and several other protein subunits (Figure 1). Human m 6 A writer complexes have been confirmed in vitro to only write m 6 A on a consensus RNA motif: RRACH (R = A or G; H = A, U, or C) (Liu et al, 2013); note that this sequence was identified much earlier as an m 6 A consensus sequence in mRNA (Csepany et al, 1990;Narayan et al, 1994;Narayan & Rottman, 1988). m 6 A writer complexes are essential for viability, as the knockout of METTL3 was shown to be embryo-lethal (Geula et al, 2015).…”

Section: A Methyltransferases (Writers)mentioning

confidence: 99%

“…digestion and 32 P labelling identified the consensus sequences that bear m 6 A marks as purine-m 6 A-C via (Nichols & Welder, 1981), and subsequent mutational studies and in vitro substrate preference assays using methyltransferase enzymes identified the mammalian consensus sequences as [G/A/U][G>A]m 6 AC[U>A>C] (Csepany, Lin, Baldick, & Beemon, 1990;Narayan, Ludwiczak, Goodwin, & Rottman, 1994;Narayan & Rottman, 1988).…”

mentioning

confidence: 99%

Dynamic and reversible RNA N⁶‐methyladenosine methylation

2018

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N 6 -methyladenosine (m 6 A) is the most abundant internal chemical modification in eukaryotic messenger RNAs (mRNAs). The discovery in 2011 that m 6 A is reversed by the fat mass and obesity-associated protein stimulated extensive worldwide research efforts on the regulatory biological functions of dynamic m 6 A and other RNA modifications. The epitranscriptomic mark m 6 A is written, read, and erased through the activities of a complicated network of enzymes and other proteins. m 6 A-binding proteins read m 6 A marks and transduce their downstream regulatory effects by altering RNA metabolic processes. In this review, we summarize the current knowledge of m 6 A modifications, with particular focus on the functions of its writer, eraser, and reader proteins in posttranscriptional gene regulation and discuss the impact of m 6 A marks on human health.

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Sequence specificity of mRNA N6-adenosine methyltransferase

Cited by 171 publications

References 33 publications

Roles of Long Noncoding RNAs and Circular RNAs in Translation

Roles of Long Noncoding RNAs and Circular RNAs in Translation

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

Dynamic and reversible RNA N⁶‐methyladenosine methylation

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Sequence specificity of mRNA N6-adenosine methyltransferase

Cited by 171 publications

References 33 publications

Roles of Long Noncoding RNAs and Circular RNAs in Translation

Roles of Long Noncoding RNAs and Circular RNAs in Translation

RNA Demethylase FTO Mediated RNA m6A Modification Is Involved in Maintaining Maternal-Fetal Interface in Spontaneous Abortion

Dynamic and reversible RNA N6‐methyladenosine methylation

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Dynamic and reversible RNA N⁶‐methyladenosine methylation