Collection |

The Epitranscriptome

A role for DNA modification in gene regulation is well established, but much less is known about how RNA modification affects RNA fate and influences the way genes are expressed. This web collection features articles from various Nature journals that highlight this exciting new research area of ‘epitranscriptomics’.

We hope you will enjoy the read!

Illustration by Viktor Koen based on concepts developed for Gidi Rechavi’s group, Sheba Medical Center, Tel Aviv University.

Reviews, News and Comment

As researchers open up to the reality of RNA modification, an expanded epitranscriptomics toolbox takes shape.

Technology Feature | | Nature

Although it has been known for decades that RNA is subjected to numerous covalent modifications, there has been a recent surge in interest driven by sequencing-based transcriptome-wide detection methods and the realization that RNA modifications have important roles in diverse biological processes. This Review describes the range of detection strategies for RNA modifications, their particular strengths and limitations, and how responsible and complementary application of these techniques will be required to ensure the quality and interpretability of the rapidly accumulating data sets.

Review Article | | Nature Reviews Genetics

Reversible mRNA methylation is an emerging mode of eukaryotic post-transcriptional gene regulation. N6-methyladenosine (m6A) affects mRNA processing, translation and decay during cell differentiation, embryonic development and stress responses. Other mRNA modifications — N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine — together with m6A code a new layer of information that controls protein synthesis.

Review Article | | Nature Reviews Molecular Cell Biology

Pseudouridine is the most abundant internal post-transcriptional modification of spliceosomal small nuclear RNAs and ribosomal RNAs. Transcriptome-wide maps of RNA pseudouridylation have recently established that pseudouridines are also found in mRNAs, potentially representing a new mechanism of proteomic diversification.

Progress | | Nature Reviews Molecular Cell Biology

The results of transcriptome-wide N6-methyladenosine (m6A) mapping techniques have resolved many of the long-standing concerns regarding the physiological relevance of m6A, which suggests that this modification regulates mRNA fate and function. The identification of adenosine methylases and demethylases provides insights into the cellular pathways that involve m6A and indicates a role of m6A in physiological processes.

Review Article | | Nature Reviews Molecular Cell Biology

Post-transcriptional RNA modifications can be dynamic and might have functions beyond fine-tuning the structure and function of RNA. Understanding these RNA modification pathways and their functions may allow researchers to identify new layers of gene regulation at the RNA level.

Commentary | | Nature Chemical Biology

Primary Research

Here the m1A modification is discovered in messenger RNA and mapped at the transcriptome-wide level; the modification is conserved, dynamic, accumulates in structured regions around translation initiation sites upstream of the first splice site, and correlates with higher protein expression.

Article | | Nature

Under stress, such as heat shock, the N6-methyladenosine (m6A) modification is shown to accumulate primarily in the 5′ untranslated region of induced mRNAs owing to the translocation of an m6A interacting protein, YTHDF2, into the nucleus, resulting in increased cap-independent translation of these mRNAs, indicating one possible mechanism by which stress-responsive genes can be preferentially expressed.

Letter | | Nature

The addition of the N6-methyladenosine (m6A) mark to primary microRNAs by METTL3 in mammalian cells is found to promote the recognition of these microRNA precursors by DGCR8, a component of the microprocessor complex.

Letter | | Nature

The single-stranded nature of RNAs synthesized in the cell gives them great scope to form different structures, but current methods to measure RNA structure in vivo are limited; now, a new methodology allows researchers to examine all four nucleotides in mouse embryonic stem cells.

Letter | | Nature

N6-methyladenosine (m6A) is an abundant internal modification of messenger RNA (mRNA) that has been reported recently in thousands of mammalian mRNAs and long non-coding RNAs (lncRNAs). Zhao and colleagues identify two methyltransferases responsible for this modification in mammalian cells, and demonstrate that they are required for embryonic stem cell self-renewal maintenance through an effect of the modification on the degradation of developmental regulator transcripts.

Letter | | Nature Cell Biology

Modification of mRNA with N 6-methyladenosine (m6A) is proposed to regulate transcript stability. Here, Jia et al. uncover plant-specific features in the m6A methylome of Arabidopsis, such as methylation enrichment around the start codon, and suggest a positive role in gene expression.

Article | | Nature Communications

The modification of uridine to pseudouridine is widespread in transfer and ribosomal RNAs but not observed so far in a coding RNA; here a new technique is used to detect this modification on a genome-wide scale, leading to the identification of pseudouridylation in messenger RNAs as well as almost 100 new sites in non-coding RNAs.

Letter | | Nature

The mRNAs of higher eukaryotes are extensively modified internally with N6-methyladenosine, but the specific functional role of this modification has been unclear; here this modification on mRNA is shown to be recognized by several proteins, the modification and its recognition serve to regulate the RNA’s lifetime.

Letter | | Nature

N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNA; here the human and mouse m6A modification landscape is presented in a transcriptome-wide manner, providing insights into this epigenetic modification.

Article | | Nature