RNA modification articles within Nature Communications

Featured

• Article
  18 April 2024 | Open Access

  Detecting m⁶A at single-molecular resolution via direct RNA sequencing and realistic training data

  Direct RNA-seq offers the possibility to identify RNA modifications on single molecules. Here, the authors report on the synthesis of biologically realistic training data and the development of mAFiA that accurately detects m⁶A on single read level.

  • Adrian Chan
  • , Isabel S. Naarmann-de Vries
  •  & Christoph Dieterich

• Article
  13 March 2024 | Open Access

  Toll/interleukin-1 receptor (TIR) domain-containing proteins have NAD-RNA decapping activity

  Toll/interleukin-1 receptor domain-containing proteins can catabolize NAD⁺. Here, Wang et al show that these proteins can also function as NAD-RNA decapping enzymes by releasing the NAM moiety from the NAD-RNA, resulting in the regulation of gene expression.

  • Xufeng Wang
  • , Dongli Yu
  •  & Xuemei Chen

• Article
  22 January 2024 | Open Access

  LOX-1 acts as an N⁶-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase

  N⁶-methyladenosine (m⁶A) modification of mRNA regulates gene expression in eukaryotes. Here, Zeng et al. show that m⁶A modification of mRNAs contributes to protection against the pathogen Helicobacter pylori by downregulating a host protein that acts as receptor for the pathogen.

  • Judeng Zeng
  • , Chuan Xie
  •  & William K. K. Wu

• Article
  21 November 2023 | Open Access

  Identification of NAD-RNA species and ADPR-RNA decapping in Archaea

  NAD serves as a 5′-terminal cap for bacterial and eukaryotic transcripts, and can be degraded at high temperatures to generate ADP-ribose (ADPR). Here, Gomes-Filho et al. identify NAD-RNAs in thermophilic and mesophilic archaea and provide insights into NAD- and ADPR-mediated turnover of RNAs in these organisms.

  • José Vicente Gomes-Filho
  • , Ruth Breuer
  •  & Lennart Randau

• Article
  07 November 2023 | Open Access

  MePMe-seq: antibody-free simultaneous m⁶A and m⁵C mapping in mRNA by metabolic propargyl labeling and sequencing

  Methylation is the dominant modification in mRNA and occurs at a variety of sites. Here, Hartstock et al. show that a clickable analogue of the key cosubstrate S-adenosyl-L-methionine (SAM) can be produced in cells, allowing for identification and mapping of different methylated nucleosides in mRNA.

  • Katja Hartstock
  • , Nadine A. Kueck
  •  & Andrea Rentmeister

• Article
  23 October 2023 | Open Access

  Phase separation of BuGZ regulates gut regeneration and aging through interaction with m⁶A regulators

  Phase separation serves to compartmentalize and concentrate cellular components to facilitate essential physiological processes. Here, the authors elucidate the role and mechanism of BuGZ-mediated phase separation in the context of gut regeneration and aging.

  • Qiaoqiao Zhang
  • , Kai Deng
  •  & Hao Jiang

• Article
  06 October 2023 | Open Access

  YTHDF2 facilitates aggresome formation via UPF1 in an m⁶A-independent manner

  YTHDF2 has been extensively studied as an m⁶A-related RNA metabolism. Here, the authors show that YTHDF2 also contributes to protein homeostasis in an m⁶A-independent manner by promoting the formation of aggresomes through its interaction with UPF1.

  • Hyun Jung Hwang
  • , Tae Lim Park
  •  & Yoon Ki Kim

• Article
  13 July 2023 | Open Access

  Exon-intron boundary inhibits m⁶A deposition, enabling m⁶A distribution hallmark, longer mRNA half-life and flexible protein coding

  m⁶A mRNA modification is not typically found near splice junctions in mRNAs. Here the authors show exon-intron boundary inhibits m6A deposition at ~100 nt region nearby splice site, enabling m⁶A distribution hallmark, more stable mRNA and flexible protein coding.

  • Zhiyuan Luo
  • , Qilian Ma
  •  & Shengdong Ke

• Article
  27 June 2023 | Open Access

  K235 acetylation couples with PSPC1 to regulate the m⁶A demethylation activity of ALKBH5 and tumorigenesis

  Deregulation of N6-methyladenosine (m6A) modification can contribute to the pathogenesis of cancers. Here the authors show that m6A demethylase ALKBH5 is acetylated at K235 by acetyltransferase KAT8 and interacts with RNA-binding protein PSCP1 to enhance m6A demethylation and promote tumorigenesis.

  • Xiao-Lan Zhang
  • , Xin-Hui Chen
  •  & Guang-Rong Yan

• Article
  22 June 2023 | Open Access

  Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice

  Generation of mature oocytes requires tight regulation of a discontinuous meiotic cell cycle. Here they show that the acetyltransferase Nat10 mediates modification of RNAs targeted for degradation and find that this process is essential for female oocyte meiosis and maturation.

  • Xue Jiang
  • , Yu Cheng
  •  & Jianqiang Bao

• Article
  05 April 2023 | Open Access

  The m⁶A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs

  Rhabdomyosarcoma (RMS) is the most diffused soft tissue sarcoma in children and adolescents. Herein, the authors identify the m⁶A machinery and the RNA helicase DDX5 as factors responsible for the increase of a subset of circRNAs in RMS, providing protein and RNA candidates for the study of its tumorigenicity.

  • Dario Dattilo
  • , Gaia Di Timoteo
  •  & Irene Bozzoni

• Article
  24 March 2023 | Open Access

  The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis

  Modification of RNA with m6A has been shown to be important during spermatogenesis. Here they identify post-transcriptional functions of PRRC2A, showing it promotes transcriptome transition from spermatogonia to spermatocytes and the translation of genes related to cell division.

  • Xinshui Tan
  • , Caihong Zheng
  •  & Fengchao Wang

• Article
  13 March 2023 | Open Access

  Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice

  Activation of white adipose tissue (WAT) thermogenesis alleviates obesity-associated metabolic disorders in rodents. Here the authors report that the m6 A RNA modification reader YTHDF1 promotes WAT thermogenesis in a study with male mice, and may be a potential target for the treatment of obesity.

  • Sujun Yan
  • , Xiaoling Zhou
  •  & Xiangwei Gao

• Article
  02 March 2023 | Open Access

  rRNA methylation by Spb1 regulates the GTPase activity of Nog2 during 60S ribosomal subunit assembly

  Regulation of 60S biogenesis remains poorly understood. Using cryo-EM, the authors show that failure of Spb1 to methylate the A-loop nucleotide G2922  prematurely activates the GTPase Nog2, suggesting that Spb1 and Nog2 form a kinetic checkpoint during ribosome maturation.

  • Kamil Sekulski
  • , Victor Emmanuel Cruz
  •  & Jan P. Erzberger

• Article
  01 March 2023 | Open Access

  Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment

  m6A modification has been reported to play roles in many developmental and pathological processes, but its role in AKI remains poorly understood. Here, the authors show the role and the mechanism of the m6A demethylase, ALKBH5 on IRI induced AKI.

  • Juntao Chen
  • , Cuidi Xu
  •  & Tongyu Zhu

• Article
  16 February 2023 | Open Access

  Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

  Th17 cells produce a range of characteristic Th17 type cytokines and express transcription factors governed by epigenetic regulation to engage the Th17 programme. Here the authors implicate the RNA 5- methylcytosine (m⁵C) methyltransferase Nsun2 in Th17 cells and the promotion of colitis in a murine model.

  • Wen-Lan Yang
  • , Weinan Qiu
  •  & Yun-Gui Yang

• Article
  23 December 2022 | Open Access

  Exon junction complex shapes the m⁶A epitranscriptome

  Here the authors show the exon junction complex (EJC) component, EIF4A3, locally restricts METTL3- mediated mRNA methylation at exon junctions to explain the observed widespread enrichment of m6A modification in 3’ untranslated regions.

  • Xin Yang
  • , Robinson Triboulet
  •  & Richard I. Gregory

• Article
  05 December 2022 | Open Access

  Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G

  Interaction between APOBEC3G and RNA is critical for its antiviral function. Here, the authors report four co-crystal structures of rhesus macaque APOBEC3G and RNA, demonstrating unpaired AA and GA dinucleotide motifs are preferentially recognized.

  • Hanjing Yang
  • , Kyumin Kim
  •  & Xiaojiang S. Chen

• Article
  09 November 2022 | Open Access

  METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury

  The benefit of regular exercise on the heart has been well documented but the role of RNA m⁶A modification in exercise-induced cardiac remodelling remains largely unknown. In this study, the authors report that METTL14 plays an important role in RNA m⁶A modification in exercise-induced physiological cardiac hypertrophy.

  • Lijun Wang
  • , Jiaqi Wang
  •  & Junjie Xiao

• Article
  04 October 2022 | Open Access

  Autophagy induction promoted by m⁶A reader YTHDF3 through translation upregulation of FOXO3 mRNA

  The role of eiptranscriptomic modifications in autophagy is unclear. Here, the authors show that the m⁶A reader YTHDF3 functions as a nutrient responder to recognize upregulated m⁶A modification, promoting FOXO3 translation to subsequently initiate autophagy.

  • WeiChao Hao
  • , MeiJuan Dian
  •  & Dong Xiao

• Article
  26 September 2022 | Open Access

  Structural insights into molecular mechanism for N⁶-adenosine methylation by MT-A70 family methyltransferase METTL4

  Here the authors combine functional and structural work to show that METTL4 functions as U2 snRNA m6Am RNA methyltransferase supporting N6-methylation of 2’-O-methyladenosine in Arabidopsis.

  • Qiang Luo
  • , Jiezhen Mo
  •  & Jinbiao Ma

• Article
  07 September 2022 | Open Access

  TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance

  The authors reveal insights into miRNA tailing specificity of TENTs and their effect on miRNA levels by combinatory KOs of TENT2, TUT4 and TUT7. They show uridylation is linked to TENT2 and identify non-redundant functions between TUT4 and TUT7.

  • Acong Yang
  • , Xavier Bofill-De Ros
  •  & Shuo Gu

• Article
  18 July 2022 | Open Access

  N⁶-methyladenosine modification-mediated mRNA metabolism is essential for human pancreatic lineage specification and islet organogenesis

  Ma et al. profile the dynamic landscape of m⁶A during pancreatic differentiation, and identify ALKBH5 as an essential m⁶A regulator supporting pancreatic differentiation, indicating a role for m⁶A-mediated mRNA metabolism in cell-fate specification.

  • Xiaojie Ma
  • , Jie Cao
  •  & Saiyong Zhu

• Article
  29 June 2022 | Open Access

  Limited effects of m⁶A modification on mRNA partitioning into stress granules

  Recent studies proposed that m⁶A modification in mammalian mRNAs increases their recruitment to stress granule. However, here the authors observed that m⁶A modification has a limited effect on mRNA entry into stress granules.

  • Anthony Khong
  • , Tyler Matheny
  •  & Roy Parker

• Article
  17 May 2022 | Open Access

  Deep learning modeling m⁶A deposition reveals the importance of downstream cis-element sequences

  The site specificity of m6A mRNA modification is a fundamental RNA biology question. Here, Luo et al., develop the iM6A, a deep learning method to model this process, showing that its site-specificity is determined by the primary nucleotide sequence.

  • Zhiyuan Luo
  • , Jiacheng Zhang
  •  & Shengdong Ke

• Article
  06 May 2022 | Open Access

  Regulation of A-to-I RNA editing and stop codon recoding to control selenoprotein expression during skeletal myogenesis

  Stop codon recoding is a unique mechanism for selenoprotein biogenesis. Here, the authors report regulatory systems for selenoprotein expression during skeletal muscle differentiation by regulating A-to-I RNA editing and stop codon recoding.

  • Yuta Noda
  • , Shunpei Okada
  •  & Tsutomu Suzuki

• Article
  05 May 2022 | Open Access

  Developmental mRNA m⁵C landscape and regulatory innovations of massive m⁵C modification of maternal mRNAs in animals

  mRNAs are known to be decorated with m5C at a low-to-medium level. Here, the authors generate atlases of mRNA m5C during animal development in 6 species and identify convergent and unexpected massive methylation of maternal mRNAs by NSUN2 and NSUN6.

  • Jianheng Liu
  • , Tao Huang
  •  & Rui Zhang

• Article
  03 May 2022 | Open Access

  Pytheas: a software package for the automated analysis of RNA sequences and modifications via tandem mass spectrometry

  RNA modifications represent a critical aspect of RNA biology that is not well suited to sequencing methods. Here, the authors provide a software tool for automated analysis of RNA tandem mass spectra with full support of modifications, isotope labelling, and control of false discovery rate.

  • Luigi D’Ascenzo
  • , Anna M. Popova
  •  & James R. Williamson

• Article
  20 April 2022 | Open Access

  TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer

  RNA modifications are important regulators of RNA biology. Here we report N¹-methyladenosine (m¹A) enrichment on 22-nucleotide tRNA fragments and its effect on gene-silencing. Higher level of m¹A in bladder cancer is accompanied by gene dysregulation in unfolded protein response.

  • Zhangli Su
  • , Ida Monshaugen
  •  & Anindya Dutta

• Article
  18 March 2022 | Open Access

  WTAP-mediated m⁶A modification of lncRNA NORAD promotes intervertebral disc degeneration

  Intervertebral disc degeneration (IVDD) is the leading cause of low back pain and Nucleus pulposus cell senescence contributes a lot to its progression. Here, the authors reveal WTAP-mediated m6A modification of lncRNA NORAD promotes IVDD.

  • Gaocai Li
  • , Liang Ma
  •  & Cao Yang

• Article
  08 March 2022 | Open Access

  CMTr cap-adjacent 2′-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

  The two cap methyltransferases (CMTrs) redundantly methylate riboses of first cap adjacent nucleotides in messenger RNAs in Drosophila. Here, CMTrs are required for reward learning and localization of untranslated messenger RNAs to synapses.

  • Irmgard U. Haussmann
  • , Yanying Wu
  •  & Matthias Soller

• Article
  02 March 2022 | Open Access

  Two zinc finger proteins with functions in m⁶A writing interact with HAKAI

  The components of m⁶A writer and their interactions are still far from fully understood. Here, the authors identify two HAKAI-interacting zinc finger proteins, HIZ1 and HIZ2, as components of the Arabidopsis m⁶A writer complex, and show that hiz2 mutant plants have an 85% reduction in m⁶A abundance and severe developmental defects.

  • Mi Zhang
  • , Zsuzsanna Bodi
  •  & Rupert G. Fray

• Article
  25 January 2022 | Open Access

  Parallel functional assessment of m⁶A sites in human endodermal differentiation with base editor screens

  N6-methyladenosine (m⁶A) plays important role in lineage specifications of embryonic stem cells, but its role at specific sites has not been assessed. Here the authors develop an adenine editor-based strategy, and systematically identify functional m⁶A sites that control lineage decisions in human embryonic stem cells.

  • Weisheng Cheng
  • , Fang Liu
  •  & Jinkai Wang

• Article
  10 January 2022 | Open Access

  Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance

  Different mechanisms have been reported to explain resistance to chemotherapy in cancer. Here, the authors show that the chemotherapeutic drug 5-fluorouracil alters the function of ribosomes to promote pro-survival gene translation leading to chemotherapy resistance.

  • Gabriel Therizols
  • , Zeina Bash-Imam
  •  & Jean-Jacques Diaz

• Article
  10 December 2021 | Open Access

  Dynamic regulation of N⁶,2′-O-dimethyladenosine (m⁶Am) in obesity

  m6A and m6Am are two prevalent mRNA modifications which are target for removal by the fat mass and obesity gene FTO. Here the authors capture the differential profile of these two modifications in the liver of obese mice and identify dynamic translation regulation by the m6Am modification.

  • Moshe Shay Ben-Haim
  • , Yishay Pinto
  •  & Gideon Rechavi

• Article
  26 November 2021 | Open Access

  Fat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice

  Post-transcriptional modification of RNA can contribute to regulating behavior. Here, the authors show that modulating the expression of Fto results in epitranscriptomic changes in the mouse hippocampus associated with depression-like behavior.

  • Shu Liu
  • , Jianbo Xiu
  •  & Qi Xu

• Article
  18 June 2021 | Open Access

  Hakai is required for stabilization of core components of the m⁶A mRNA methylation machinery

  The E3 ligase Hakai can interact with the m⁶A methylation machinery but its function is still unclear. Here, the authors show that Hakai is a conserved component of the m⁶A methyltransferase complex and provide functional and molecular insights into its role in regulating m⁶A levels in Drosophila.

  • Praveen Bawankar
  • , Tina Lence
  •  & Jean-Yves Roignant

• Article
  18 June 2021 | Open Access

  Arginine methylation of METTL14 promotes RNA N⁶-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells

  The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m⁶A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m⁶A methylation activity of the complex.

  • Xiaona Liu
  • , Hailong Wang
  •  & Shan Xiao

• Article
  28 May 2021 | Open Access

  A single m⁶A modification in U6 snRNA diversifies exon sequence at the 5’ splice site

  Spliceosomal U6 snRNA is modified by m⁶A. Here the authors show that m⁶A modification on U6 snRNA promotes efficient recognition of the splice site through cooperating with U5 snRNA, indicating that U6 snRNA m⁶A allows the 5’ exon sequence variation.

  • Yuma Ishigami
  • , Takayuki Ohira
  •  & Tsutomu Suzuki

• Article
  12 April 2021 | Open Access

  Role of Hakai in m⁶A modification pathway in Drosophila

  Drosophila m6A writer complex regulates alternative splicing of the Sex-lethal gene. Here the authors show that a potential E3 ligase Hakai interacts with the fly m6A writer complex and that m6A level is reduced in Hakai mutant flies.

  • Yanhua Wang
  • , Lifeng Zhang
  •  & Dong Yan

• Article
  19 March 2021 | Open Access

  R-loop resolution promotes co-transcriptional chromatin silencing

  Nascent non-coding RNA can mediate chromatin silencing, however mechanistically this process is poorly understood. Here the authors show that resolution of an R-loop during 3'-end processing of a plant antisense transcript recruits chromatin modifiers to promote chromatin silencing.

  • Congyao Xu
  • , Zhe Wu
  •  & Caroline Dean

• Article
  05 March 2021 | Open Access

  A neural m⁶A/Ythdf pathway is required for learning and memory in Drosophila

  Epitranscriptomic modifications can regulate learning and memory. Here, the authors provide proteomic and functional analysis of N6-methyladenosine (m⁶A)-binding proteins in D. melanogaster and unveil behavioral and regulatory defects for m6A/Ythdf mutants.

  • Lijuan Kan
  • , Stanislav Ott
  •  & Eric C. Lai

• Article
  09 February 2021 | Open Access

  L1 retrotransposons exploit RNA m⁶A modification as an evolutionary driving force

  L1 is a group of active retrotransposons in humans. Here the authors show that m⁶A modifications on L1 RNA increase translation efficiency and retrotransposition in human cells. M⁶A motifs are more enriched in evolutionary young L1s.

  • Sung-Yeon Hwang
  • , Hyunchul Jung
  •  & Kwangseog Ahn

• Article
  15 January 2021 | Open Access

  Cell culture NAIL-MS allows insight into human tRNA and rRNA modification dynamics in vivo

  Post transcriptional modification of RNAs represents an important layer of gene regulation. Here the authors describe NAIL-MS—a method for monoisotopic RNA labeling in cell culture—demonstrating its capabilities by analyzing the modification kinetics of total tRNA, 18S rRNA and tRNA^Phe as models.

  • Matthias Heiss
  • , Felix Hagelskamp
  •  & Stefanie Kellner

• Article
  04 December 2020 | Open Access

  A substrate binding model for the KEOPS tRNA modifying complex

  KEOPS is an evolutionary conserved complex with a core of four core subunits—Pcc1, Kae1, Bud32 and Cgi121—that catalyzes the universal and essential tRNA modification N⁶-threonylcarbamoyl adenosine (t⁶A). Here the authors describe a Cgi121-tRNA crystal structure and new composite model of the KEOPS holo-enzyme-substrate complex that shed light on the t⁶A catalytic cycle and its regulation.

  • Jonah Beenstock
  • , Samara Mishelle Ona
  •  & Frank Sicheri

• Article
  28 August 2020 | Open Access

  Complete chemical structures of human mitochondrial tRNAs

  Mitochondrial tRNA modifications are important for tRNA stability and accurate decoding. By employing RNA mass spectrometry and deep sequencing, here the authors provide a comprehensive analysis of post-transcriptional modifications of 22 species of human mitochondrial tRNAs.

  • Takeo Suzuki
  • , Yuka Yashiro
  •  & Tsutomu Suzuki

• Article
  05 June 2020 | Open Access

  m⁵C modification of mRNA serves a DNA damage code to promote homologous recombination

  Post-translational modifications of proteins at DNA damage sites can facilitate the recruitment of DNA repair factors. Here, the authors show that mRNA is locally modified with m⁵C at sites of DNA damage by the RNA methyltransferase TRDMT1 to promote homologous recombination repair.

  • Hao Chen
  • , Haibo Yang
  •  & Li Lan

• Article
  19 May 2020 | Open Access

  DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification

  METTL2 methyltransferase is responsible for 3-methylcytosine modification of arginine tRNAs in mammals. Here the authors show that DALR anticodon binding domain containing 3 (DALRD3) forms a complex with METTL2 to recognize specific arginine tRNAs and find DALRD3 mutations in patients with developmental delay and early-onset epileptic encephalopathy.

  • Jenna M. Lentini
  • , Hessa S. Alsaif
  •  & Dragony Fu

• Article
  27 April 2020 | Open Access

  Immunoglobulin expression and the humoral immune response is regulated by the non-canonical poly(A) polymerase TENT5C

  Regulating polyadenylation is important for mRNA stability, which can in turn affect B cell maturation and humoral immune responses. Here the authors use Nanopore poly(A) sequencing to explore the importance of the cytoplasmic poly(A) polymerase TENT5C, particularly in the production of immunoglobulins.

  • Aleksandra Bilska
  • , Monika Kusio-Kobiałka
  •  & Seweryn Mroczek

• Article
  26 February 2020 | Open Access

  Dinucleoside polyphosphates act as 5′-RNA caps in bacteria

  Nicotinamide adenine dinucleotide and coenzyme A serve as a 5′-cap of prokaryotic RNA. Here the authors report that methylated and non-methylated dinucleoside polyphosphates (Np_nNs) exist as Escherichia coli RNA caps which can be cleaved by 5′-pyrophosphohydrolase (RppH) and bis(5′-nucleosyl)-tetraphosphatase (ApaH).

  • Oldřich Hudeček
  • , Roberto Benoni
  •  & Hana Cahová