Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex

Bokar, Joseph A.; Rath-Shambaugh, Mary Eileen; Ludwiczak, R L; Narayan, Prema; Rottman, Fritz M.

doi:10.1016/s0021-9258(17)32497-3

Cited by 326 publications

(238 citation statements)

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“…The ubiquitous presence of modified nucleotides in all kinds of RNA transcripts (both coding and non-coding) has given rise to a completely new concept named 'Epithanscriptomics' [1,2]. Among all the modifications m 6 A is the most abundant internal modification of mRNAs and long noncoding RNAs (lncRNAs). In mRNAs, m 6 A sites are highly enriched in 5′-untranslated regions (5′-UTRs), near the stop codons, in the 3′-untranslated regions (3′-UTRs) and within long internal exons.…”

Section: Introductionmentioning

confidence: 99%

“…Among all the modifications m 6 A is the most abundant internal modification of mRNAs and long noncoding RNAs (lncRNAs). In mRNAs, m 6 A sites are highly enriched in 5′-untranslated regions (5′-UTRs), near the stop codons, in the 3′-untranslated regions (3′-UTRs) and within long internal exons. m 6 A most frequently occurs in the consensus sequence RRACH (R = G/A/U, A = m 6 A, H=U/A/C) and such sequence occurs about every 85 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

“…In mRNAs, m 6 A sites are highly enriched in 5′-untranslated regions (5′-UTRs), near the stop codons, in the 3′-untranslated regions (3′-UTRs) and within long internal exons. m 6 A most frequently occurs in the consensus sequence RRACH (R = G/A/U, A = m 6 A, H=U/A/C) and such sequence occurs about every 85 nucleotides. Thus, the frequency of m 6 A has been estimated as 3-5 sites per mRNA transcript and 0.1-0.4% of all adenosine nucleotides in mammalian mRNAs [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…m 6 A most frequently occurs in the consensus sequence RRACH (R = G/A/U, A = m 6 A, H=U/A/C) and such sequence occurs about every 85 nucleotides. Thus, the frequency of m 6 A has been estimated as 3-5 sites per mRNA transcript and 0.1-0.4% of all adenosine nucleotides in mammalian mRNAs [3,4]. Due to vital functions of m 6 A modification that are observed in multiple cellular processes, dysregulation of the modification and its regulators have been implicated in various human diseases, especially in different types of cancers as reviewed in recent literatures [3,5].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the frequency of m 6 A has been estimated as 3-5 sites per mRNA transcript and 0.1-0.4% of all adenosine nucleotides in mammalian mRNAs [3,4]. Due to vital functions of m 6 A modification that are observed in multiple cellular processes, dysregulation of the modification and its regulators have been implicated in various human diseases, especially in different types of cancers as reviewed in recent literatures [3,5]. Here we discussed recent findings that demonstrate the role of m 6 A in modulating cellular oncogenic signaling pathways leading to carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

2021

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The m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

2021

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FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications

2018

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The fate of mRNA is regulated by epitranscriptomic nucleotide modifications, the most abundant of which is N -methyladenosine (m A). Although the pattern and distribution of m A in mRNA is mediated by specific methyltransferases, a recent hypothesis is that specific demethylases or 'erasers' allow m A to be dynamically reversed by signaling pathways. In this Review, we discuss the data in support and against this model. New insights into the function of fat mass and obesity-associated protein (FTO), the original enzyme thought to be an m A eraser, reveal that its physiologic target is not m A, but instead is N ,2'-O-dimethyladenosine (m A ). Another m A demethylase, ALKBH5, appears to have functions limited to sperm development in normal mice. Overall, the majority of the data suggest that m A is generally not reversible, although m A may be susceptible to demethylation in pathophysiological states such as cancer.

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METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5

Zhou

Tang

Xu³

et al. 2021

Molecular Oncology

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N6-methyladenosine (m6A) has emerged as the most prevalent post-transcriptional modification on mRNA that contributes prominently to tumorigenesis. However, the specific function of m6A methyltransferase methyltransferase-like 3 (METTL3) in colorectal cancer (CRC) remains elusive. Herein, we explored the biological function of METTL3 in CRC progression. Clinically, METTL3 was frequently upregulated in CRC tissues, cell lines, and plasma samples and its high expression predicted poor prognosis of CRC patients. Functionally, knockdown of METTL3 significantly repressed CRC cell proliferation and migration in vitro, while its overexpression accelerated CRC tumor formation and metastasis both in vitro and in vivo. Mechanistically, METTL3 epigenetically repressed YPEL5 in an m6A-YTHDF2-dependent manner by targeting the m6A site in the coding sequence region of the YPEL5 transcript. Moreover, overexpression of YPEL5 significantly reduced CCNB1 and PCNA expression. Collectively, we identified the pivotal role of METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing YPEL5 expression in an m6A-YTHDF2-dependent manner, suggesting a promising strategy for the diagnosis and therapy of CRC.

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Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex

Cited by 326 publications

References 46 publications

The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications

METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5

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Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex

Cited by 326 publications

References 46 publications

The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

FTO, m6Am, and the hypothesis of reversible epitranscriptomic mRNA modifications

METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5

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FTO, m⁶A_m, and the hypothesis of reversible epitranscriptomic mRNA modifications