Genetic analyses support the contribution of mRNA N6-methyladenosine (m6A) modification to human disease heritability

et al. 2020

Front. Cell Dev. Biol.

N 6-methyladenosine (m 6 A) is the most abundant post-transcriptional modification in mRNA, and regulates critical biological functions via m 6 A reader proteins that bind to m 6 A-containing transcripts. There exist multiple m 6 A reader proteins in the human genome, but their respective binding specificity and functional relevance under different biological contexts are not yet fully understood due to the limitation of experimental approaches. An in silico study was devised to unveil the target specificity and regulatory functions of different m 6 A readers. We established a support vector machine-based computational framework to predict the epitranscriptome-wide targets of six m 6 A reader proteins (YTHDF1-3, YTHDC1-2, and EIF3A) based on 58 genomic features as well as the conventional sequence-derived features. Our model achieved an average AUC of 0.981 and 0.893 under the full-transcript and mature mRNA model, respectively, marking a substantial improvement in accuracy compared to the sequence encoding schemes tested. Additionally, the distinct biological characteristics of each individual m 6 A reader were explored via the distribution, conservation, Gene Ontology enrichment, cellular components and molecular functions of their target m 6 A sites. A web server was constructed for predicting the putative binding readers of m 6 A sites to serve the research community, and is freely accessible at: http://m6areader.rnamd.com.

Section: Resultssupporting

confidence: 92%

Section: Detect Potential Substrate Of M 6 a Readerssupporting

confidence: 88%

m6A Reader: Epitranscriptome Target Prediction and Functional Characterization of N6-Methyladenosine (m6A) Readers

Zhen

et al. 2020

Front. Cell Dev. Biol.

“…Notably, it needs to be re-examined on the conclusion came only by siRNA knockdown in HeLa cells. Recently, Zhang et al (2020) proposed that the effects of m 6 A on translation are heterogeneous and context dependent. Indeed, it still needs to be investigated the complex function of YTHDFs in translation.…”

Section: Perspectivesmentioning

confidence: 99%

Roles of N6-Methyladenosine (m6A) in Stem Cell Fate Decisions and Early Embryonic Development in Mammals

Zhai

et al. 2020

Front. Cell Dev. Biol.

N6-methyladenosine (m 6 A) is one of the most abundant internal mRNA modifications, and it affects multiple biological processes related to eukaryotic mRNA. The majority of m 6 A sites are located in stop codons and 3 UTR regions of mRNAs. m 6 A regulates RNA metabolism, including alternative splicing (AS), alternative polyadenylation (APA), mRNA export, decay, stabilization, and translation. The m 6 A metabolic pathway is regulated by a series of m 6 A writers, erasers and readers. Recent studies indicate that m 6 A is essential for the regulation of gene expression, tumor formation, stem cell fate, gametogenesis, and animal development. In this systematic review, we summarized the recent advances in newly identified m 6 A effectors and the effects of m 6 A on RNA metabolism. Subsequently, we reviewed the functional roles of RNA m 6 A modification in diverse cellular bioprocesses, such as stem cell fate decisions, cell reprogramming and early embryonic development, and we discussed the potential of m 6 A modification to be applied to regenerative medicine, disease treatment, organ transplantation, and animal reproduction.

“…In this case, the author combined CPT treatment and DART-seq methodology to identify thousands of adenosine moieties exhibiting enhanced methylation upon slow-down of RNAPII. Interestingly, histone modifications, such as H3K36me3, may also contribute to the regulation of m 6 A deposition by recruiting the METTL14 subunit of the methylation complex (Huang et al, 2019;Zhang et al, 2020b). Additionally, binding of specific transcription factors can also facilitate m 6 A deposition (Barbieri et al, 2017;Zhang et al, 2020b).…”

Section: Impact Of Transcription Elongation On Translationmentioning

confidence: 99%

So close, no matter how far: multiple paths connecting transcription to mRNA translation in eukaryotes

Slobodin

Dikstein

2020

EMBO Reports

Transcription of DNA into mRNA and translation of mRNA into proteins are two major processes underlying gene expression. Due to the distinct molecular mechanisms, timings, and locales of action, these processes are mainly considered to be independent. During the last two decades, however, multiple factors and elements were shown to coordinate transcription and translation, suggesting an intricate level of synchronization. This review discusses the molecular mechanisms that impact both processes in eukaryotic cells of different origins. The emerging global picture suggests evolutionarily conserved regulation and coordination between transcription and mRNA translation, indicating the importance of this phenomenon for the fine‐tuning of gene expression and the adjustment to constantly changing conditions.