Opening New Avenues in Bioorganic Chemistry: Prof. Chuan He Receives the Tetrahedron Prize.

Prof. Chuan He was awarded the Tetrahedron Prize this year, one of the world's most prestigious prizes in organic chemistry. This In Focus briefly delves into the remarkable work of Prof.

Publisher Correction: Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DNA 5-Methylcytosine-Specific Amplification and Sequencing.

DNA 5-methylcytosine (5mC)-specific mapping has been hampered by severe DNA degradation and the presence of 5-hydroxymethylcytosine (5hmC) using the conventional bisulfite sequencing approach. Here, we present a 5mC-specific whole-genome amplification method (5mC-WGA), with which we achieved 5mC retention during DNA amplification from limited input down to 10 pg scale with limited interference from 5hmC signals, providing DNA 5mC methylome with high reproducibility and accuracy.

N-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I.

Internal N-methyladenosine (mA) modification is one of the most common and abundant modifications of RNA. However, the biological roles of viral RNA mA remain elusive. Here, using human metapneumovirus (HMPV) as a model, we demonstrate that mA serves as a molecular marker for innate immune discrimination of self from non-self RNAs.

Viral N-methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus.

N-methyladenosine (mA) is the most prevalent internal modification of mRNAs in most eukaryotes. Here we show that RNAs of human respiratory syncytial virus (RSV) are modified by mA within discreet regions and that these modifications enhance viral replication and pathogenesis. Knockdown of mA methyltransferases decreases RSV replication and gene expression whereas knockdown of mA demethylases has the opposite effect.

Histone H3 trimethylation at lysine 36 guides mA RNA modification co-transcriptionally.

DNA and histone modifications have notable effects on gene expression. Being the most prevalent internal modification in mRNA, the N-methyladenosine (mA) mRNA modification is as an important post-transcriptional mechanism of gene regulation and has crucial roles in various normal and pathological processes. However, it is unclear how mA is specifically and dynamically deposited in the transcriptome.

Publisher Correction: Post-transcriptional gene regulation by mRNA modifications.

In Figure 5, translation initiation is promoted not by the indicated protein, but by YTHDF1 (see below).

Author Correction: Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.

In the version of this Article originally published, the authors incorrectly listed an accession code as GES90642. The correct code is GSE90642 . This has now been amended in all online versions of the Article.

Long genes linked to autism spectrum disorders harbor broad enhancer-like chromatin domains.

Genetic variants associated with autism spectrum disorders (ASDs) are enriched in genes encoding synaptic proteins and chromatin regulators. Although the role of synaptic proteins in ASDs is widely studied, the mechanism by which chromatin regulators contribute to ASD risk remains poorly understood. Upon profiling and analyzing the transcriptional and epigenomic features of genes expressed in the cortex, we uncovered a unique set of long genes that contain broad enhancer-like chromatin domains (BELDs) spanning across their entire gene bodies.

Recognition of RNA N-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.

N-methyladenosine (mA) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers, such as YTH domain-containing proteins, to regulate mRNA fate. Here, we report the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; including IGF2BP1/2/3) as a distinct family of mA readers that target thousands of mRNA transcripts through recognizing the consensus GG(mA)C sequence. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an mA-dependent manner under normal and stress conditions and therefore affect gene expression output.

METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA mA Modification.

N-methyladenosine (mA), the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs), plays critical roles in many bioprocesses. However, its functions in normal and malignant hematopoiesis remain elusive. Here, we report that METTL14, a key component of the mA methyltransferase complex, is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15;17), or t(8;21) and is downregulated during myeloid differentiation.

"Gamete On" for mA: YTHDF2 Exerts Essential Functions in Female Fertility.

In this issue of Molecular Cell, Ivanova et al. (2017) report key functions of the mA reader YTHDF2 in the regulation of mammalian development during oocyte maturation and early zygotic development.

mA Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.

The dynamic and reversible N-methyladenosine (mA) RNA modification installed and erased by N-methyltransferases and demethylases regulates gene expression and cell fate. We show that the mA demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs.

mA-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition.

The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N-methyladenosine (mA) modified, and the clearance of these maternal mRNAs is facilitated by an mA-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of mA-modified maternal mRNAs and impedes zygotic genome activation.

Post-transcriptional gene regulation by mRNA modifications.

The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N-methyladenosine (mA) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses.

Dynamics of Human and Viral RNA Methylation during Zika Virus Infection.

Infection with the flavivirus Zika (ZIKV) causes neurological, immunological, and developmental defects through incompletely understood mechanisms. We report that ZIKV infection affects viral and human RNAs by altering the topology and function of N-adenosine methylation (mA), a modification affecting RNA structure and function. mA nucleosides are abundant in ZIKV RNA, with twelve mA peaks identified across full-length ZIKV RNA.

Quantifying mammalian genomic DNA hydroxymethylcytosine content using solid-state nanopores.

5-hydroxymethylcytosine (5 hmC), the oxidized form of 5-methylcytosine (5 mC), is a base modification with emerging importance in biology and disease. However, like most epigenetic elements, it is transparent to many conventional genetic techniques and is thus challenging to probe. Here, we report a rapid solid-state nanopore assay that is capable of resolving 5 hmC with high specificity and sensitivity and demonstrate its utility in assessing global modification abundance in genomic DNA.

N(6)-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression.

The internal N(6)-methyladenosine (m(6)A) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression, which is regulated by methyltransferases (writers), demethylases (erasers), and m(6)A-binding proteins (readers) in cells. The YTH domain family proteins (YTHDF1-3) bind to m(6)A-modified cellular RNAs and affect RNA metabolism and processing. Here, we show that YTHDF1-3 proteins recognize m(6)A-modified HIV-1 RNA and inhibit HIV-1 infection in cell lines and primary CD4(+) T-cells.

Nucleic Acid Modifications in Regulation of Gene Expression.

Nucleic acids carry a wide range of different chemical modifications. In contrast to previous views that these modifications are static and only play fine-tuning functions, recent research advances paint a much more dynamic picture. Nucleic acids carry diverse modifications and employ these chemical marks to exert essential or critical influences in a variety of cellular processes in eukaryotic organisms.

N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.

N(6)-methyladenosine (m(6)A) is the most abundant internal modification in mammalian mRNA. This modification is reversible and non-stoichiometric and adds another layer to the dynamic control of mRNA metabolism. The stability of m(6)A-modified mRNA is regulated by an m(6)A reader protein, human YTHDF2, which recognizes m(6)A and reduces the stability of target transcripts.