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Article
| Open Access
Autonomous transposons tune their sequences to ensure somatic suppression
SAFB proteins protect genome integrity by preventing retrotransposition of L1 elements yet maintaining splicing integrity, via prevention of the exonization of previously integrated transposable elements, a major constituent of human genes.
- İbrahim Avşar Ilık
- , Petar Glažar
- & Tuğçe Aktaş
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Article
| Open Access
Structural basis of ribosomal 30S subunit degradation by RNase R
Cryo-electron microscopy structures of intermediates formed during the degradation of the 30S ribosomal unit shed light on how the 3′ to 5′ exonuclease ribonuclease R controls the ribosomal degradation process.
- Lyudmila Dimitrova-Paternoga
- , Sergo Kasvandik
- & Helge Paternoga
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Hepatitis C virus RNA is 5′-capped with flavin adenine dinucleotide
Hepatitis C virus utilizes flavin adenine dinucleotide as a non-canonical initiating nucleotide for the viral RNA polymerase, resulting in 5′ capping of viral RNA, which provides protection against the host innate immune response.
- Anna V. Sherwood
- , Lizandro R. Rivera-Rangel
- & Jeppe Vinther
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Article
| Open Access
Structural basis of catalytic activation in human splicing
Cryogenic electron microscopy images of a spliceosome complex undergoing catalytic activation provide mechanistic insight into how the two ATP-dependent RNA helicases involved in this process, PRP2 and Aquarius, work together.
- Jana Schmitzová
- , Constantin Cretu
- & Vladimir Pena
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mRNA recognition and packaging by the human transcription–export complex
Cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNA ribonucleoprotein complexes bound to the transcription–export complex reveal how mRNAs are packaged and recognized for nuclear export.
- Belén Pacheco-Fiallos
- , Matthias K. Vorländer
- & Clemens Plaschka
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Article
| Open Access
RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
Analysis of messenger RNA splicing in a large cohort of pancreatic ductal adenocarcinoma tumours identifies differential splicing correlating with disease progression, associated with the the splicing regulator RBFOX2.
- Amina Jbara
- , Kuan-Ting Lin
- & Rotem Karni
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mRNA ageing shapes the Cap2 methylome in mammalian mRNA
Cap2 methylation increases on transcripts as they age, reducing activation of innate immunity.
- Vladimir Despic
- & Samie R. Jaffrey
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Article |
Structures and mechanisms of tRNA methylation by METTL1–WDR4
Using cryo-electron microscopy, structural and mechanistic insights into how the METTL1–WDR4 complex catalyses methylation of tRNAs are shown.
- Victor M. Ruiz-Arroyo
- , Rishi Raj
- & Yunsun Nam
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Article
| Open Access
Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA
RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.
- Oleg Dmytrenko
- , Gina C. Neumann
- & Chase L. Beisel
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Article
| Open Access
Structure of the OMEGA nickase IsrB in complex with ωRNA and target DNA
The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.
- Seiichi Hirano
- , Kalli Kappel
- & Feng Zhang
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Programmable RNA sensing for cell monitoring and manipulation
RNA sensing-mediated payload expression provides a specific, versatile, simple and generalizable means of detecting and manipulating animal cells with broad potential applications.
- Yongjun Qian
- , Jiayun Li
- & Z. Josh Huang
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CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1
CDK11 associates with SF3B1 and phosphorylates threonine residues at the N terminus of SF3B1 during spliceosome activation, and the inhibition of CDK11 blocks the activation and leads to widespread intron retention and the accumulation of non-functional spliceosomes on pre-mRNAs and chromatin.
- Milan Hluchý
- , Pavla Gajdušková
- & Dalibor Blazek
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RNA editing underlies genetic risk of common inflammatory diseases
cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases.
- Qin Li
- , Michael J. Gloudemans
- & Jin Billy Li
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Article
| Open Access
Reversible RNA phosphorylation stabilizes tRNA for cellular thermotolerance
Reversible internal RNA phosphrylation contributes to thermal stability and nuclease resistance of tRNA, and cellular thermotolerance of hyperthermophiles.
- Takayuki Ohira
- , Keiichi Minowa
- & Tsutomu Suzuki
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Breakage of cytoplasmic chromosomes by pathological DNA base excision repair
DNA damage during chromothripsis is caused by deoxyinosine formation on accumulated RNA–DNA hybrids in micronuclei that are then recognized by N-methyl-purine DNA glycosylase and cleaved by apurinic/apyrimidinic endonuclease.
- Shangming Tang
- , Ema Stokasimov
- & David Pellman
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Article
| Open Access
Rixosomal RNA degradation contributes to silencing of Polycomb target genes
The rixosome associates with Polycomb repressive complexes and chromatin and has a role in silencing of Polycomb target gene expression in human cells via degradation of nascent RNA transcripts.
- Haining Zhou
- , Chad B. Stein
- & Danesh Moazed
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N6-methyladenosine in poly(A) tails stabilize VSG transcripts
N6-methyladenosine is enriched in poly(A) tails of VSG transcripts in Trypanosoma brucei, and when lacking result in mRNA degradation.
- Idálio J. Viegas
- , Juan Pereira de Macedo
- & Luisa M. Figueiredo
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Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue
Bacterial MutS2, a paralogue of the DNA mismatch-repair protein MutS, is found to bind collided ribosomes and function in translational quality control.
- Federico Cerullo
- , Sebastian Filbeck
- & Claudio A. P. Joazeiro
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Cryo-EM structures of full-length Tetrahymena ribozyme at 3.1 Å resolution
Cryo-electron microscopy has been used to determine the structure of the Tetrahymena ribozyme (a catalytic RNA) at sufficiently high resolution to model side chains and metal ions.
- Zhaoming Su
- , Kaiming Zhang
- & Wah Chiu
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Article
| Open Access
Structural insights into how Prp5 proofreads the pre-mRNA branch site
The cryo-electron microscopy structure of a newly identified, early spliceosomal complex reveals the mechanism by which the RNA helicase Prp5 enhances the fidelity of the excision of introns from precursor mRNAs.
- Zhenwei Zhang
- , Norbert Rigo
- & Reinhard Lührmann
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Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia
Treatment with a specific inhibitor of the N6-methyladenosine methyltransferase METTL3 leads to reduced growth of cancer cells, indicating the potential of approaches targeting RNA-modifying enzymes for anticancer therapy.
- Eliza Yankova
- , Wesley Blackaby
- & Tony Kouzarides
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METTL3 regulates heterochromatin in mouse embryonic stem cells
Binding of METTL3 to chromatin is enriched over IAP family endogenous retroviral elements in mouse embryonic stem cells, helping to ensure the integrity of heterochromatin at these elements.
- Wenqi Xu
- , Jiahui Li
- & Hongjie Shen
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m6A RNA methylation regulates the fate of endogenous retroviruses
A CRISPR screen in mouse embryonic stem cells shows that transcripts derived from endogenous retroviruses are destabilized by m6A RNA methylation.
- Tomasz Chelmicki
- , Emeline Roger
- & Deborah Bourc’his
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Article
| Open Access
A large-scale binding and functional map of human RNA-binding proteins
A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.
- Eric L. Van Nostrand
- , Peter Freese
- & Gene W. Yeo
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Dynamic RNA acetylation revealed by quantitative cross-evolutionary mapping
A method termed ac4C-seq is introduced for the transcriptome-wide mapping of the RNA modification N4-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.
- Aldema Sas-Chen
- , Justin M. Thomas
- & Schraga Schwartz
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Molecular architecture of the human 17S U2 snRNP
The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.
- Zhenwei Zhang
- , Cindy L. Will
- & Holger Stark
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RIC-seq for global in situ profiling of RNA–RNA spatial interactions
RNA in situ conformation sequencing (RIC-seq) enables the generation of three-dimensional interaction maps of RNA in cells, which sheds light on the interactions and regulatory functions of RNA.
- Zhaokui Cai
- , Changchang Cao
- & Yuanchao Xue
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U1 snRNP regulates chromatin retention of noncoding RNAs
Long noncoding RNAs and certain unstable transcripts tend to localize to chromatin, in a process that is shown here to depend on an RNA motif that recognizes the small nuclear ribonuclear protein U1, and to rely on transcription.
- Yafei Yin
- , J. Yuyang Lu
- & Xiaohua Shen
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Spliceosomal disruption of the non-canonical BAF complex in cancer
A range of SF3B1 mutations promote tumorigenesis through the repression of BRD9, a core component of the non-canonical BAF complex, and correcting BRD9 mis-splicing in these SF3B1-mutant cells suppresses tumour growth.
- Daichi Inoue
- , Guo-Liang Chew
- & Robert K. Bradley
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Letter |
Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis
Analyses of transcriptomes from patients with acute myeloid leukaemia identified frequently co-occurring mutations of IDH2 and SRSF2, which functional analyses showed to have distinct and coordinated leukaemogenic effects on the epigenome and RNA splicing.
- Akihide Yoshimi
- , Kuan-Ting Lin
- & Omar Abdel-Wahab
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Article |
A unified mechanism for intron and exon definition and back-splicing
The cryo-electron microscopy structures of an early spliceosome complex in yeast reveal a unified mechanism for defining introns and exons and also for back-splicing to generate circular RNA.
- Xueni Li
- , Shiheng Liu
- & Rui Zhao
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Letter |
DEAD-box ATPases are global regulators of phase-separated organelles
RNA-dependent DEAD-box ATPases (DDXs) regulate the dynamics of phase-separated organelles, with ATP-bound DDXs promoting phase separation, and ATP hydrolysis inducing compartment disassembly and RNA release.
- Maria Hondele
- , Ruchika Sachdev
- & Karsten Weis
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Letter |
Rotation tracking of genome-processing enzymes using DNA origami rotors
ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.
- Pallav Kosuri
- , Benjamin D. Altheimer
- & Xiaowei Zhuang
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Letter |
Structure and function of Vms1 and Arb1 in RQC and mitochondrial proteome homeostasis
Cryo-electron microscopy structures of the yeast 60S ribosomal subunit in complex with Vms1 provides insights into the roles of proteins in the ribosome-associated quality control pathway.
- Ting Su
- , Toshiaki Izawa
- & Roland Beckmann
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Letter |
Arabidopsis FLL2 promotes liquid–liquid phase separation of polyadenylation complexes
A genetic screen for factors required by the Arabidopsis RNA-binding protein FCA identifies FLL2 as necessary in the formation of FCA nuclear bodies, and thus a role for FLL2 in liquid–liquid phase separation.
- Xiaofeng Fang
- , Liang Wang
- & Caroline Dean
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Letter |
PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components
mRNA that contains a premature termination codon (PTC) triggers a genetic compensation response that involves both transcription of its homologous genes and degradation of the mutated transcript by the nonsense-mediated decay pathway.
- Zhipeng Ma
- , Peipei Zhu
- & Jun Chen
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Letter |
Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
METTL14 recognizes the trimethyl mark on lysine 36 of histone H3 that directs m6A modifications co-transcriptionally.
- Huilin Huang
- , Hengyou Weng
- & Jianjun Chen
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Introns are mediators of cell response to starvation
Transcriptomic and genetic analyses of a deletion set of all known introns in genes of the budding yeast Saccharomyces cerevisiae indicate that introns promote resistance to starvation.
- Julie Parenteau
- , Laurine Maignon
- & Sherif Abou Elela
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Letter |
FTSJ3 is an RNA 2′-O-methyltransferase recruited by HIV to avoid innate immune sensing
HIV-1 uses the host protein FTSJ3 to methylate its own genome, thereby evading detection by the innate immune system.
- Mathieu Ringeard
- , Virginie Marchand
- & Yamina Bennasser
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Letter |
CDK12 regulates DNA repair genes by suppressing intronic polyadenylation
The kinase CDK12 suppresses usage of intronic polyadenylation sites and thereby promotes the expression of genes involved in homologous recombination DNA repair.
- Sara J. Dubbury
- , Paul L. Boutz
- & Phillip A. Sharp
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TDP-43 and RNA form amyloid-like myo-granules in regenerating muscle
Cytoplasmic, amyloid-like oligomeric assemblies that contain TDP-43 are increased in damaged tissues with elevated regeneration, thereby enhancing the possibility of amyloid fibre formation and/or aggregation of TDP-43 in disease.
- Thomas O. Vogler
- , Joshua R. Wheeler
- & Roy Parker
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Letter |
Mitochondrial double-stranded RNA triggers antiviral signalling in humans
Mitochondrial double-stranded RNA can induce an interferon response if released into the cytoplasm, but self-recognition is prevented by SUV3 helicase and PNPase exoribonuclease.
- Ashish Dhir
- , Somdutta Dhir
- & Nicholas J. Proudfoot
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Letter |
Prespliceosome structure provides insights into spliceosome assembly and regulation
The cryo-electron microscopy structure of the Saccharomyces cerevisiae prespliceosome provides insights into splice-site selection and early spliceosome assembly events.
- Clemens Plaschka
- , Pei-Chun Lin
- & Kiyoshi Nagai
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Letter |
The helicase Ded1p controls use of near-cognate translation initiation codons in 5′ UTRs
The helicase Ded1p associates with the pre-initiation complex and influences translation from near-cognate initiation codons by controlling the levels of mRNA secondary structure in 5′ untranslated regions.
- Ulf-Peter Guenther
- , David E. Weinberg
- & Eckhard Jankowsky
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Letter |
A Cdk9–PP1 switch regulates the elongation–termination transition of RNA polymerase II
The kinase Cdk9 and the phosphatase Dis2 regulate the termination of transcription in fission yeast in part by controlling the phosphorylation state of the elongation factor Spt5.
- Pabitra K. Parua
- , Gregory T. Booth
- & Robert P. Fisher
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Letter |
An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis
Loss of the ribosome-rescue factor Pelo in a subset of mouse epidermal stem cells results in hyperproliferation and altered differentiation of these cells.
- Kifayathullah Liakath-Ali
- , Eric W. Mills
- & Fiona M. Watt
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Letter |
Mitochondrial translation requires folate-dependent tRNA methylation
Mammalian mitochondria use folate-bound one-carbon units generated by the enzyme SHMT2 to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.
- Raphael J. Morscher
- , Gregory S. Ducker
- & Joshua D. Rabinowitz
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Letter |
Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells
A sequence that is frequently found in Alu elements drives the localization of some long RNAs to the nucleus in human cells.
- Yoav Lubelsky
- & Igor Ulitsky
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Article |
Visualization of chemical modifications in the human 80S ribosome structure
A high-resolution structure of the human ribosome determined by cryo-electron microscopy visualizes numerous RNA modifications that are concentrated at functional sites with an extended shell, and suggests the possibility of designing more specific ribosome-targeting drugs.
- S. Kundhavai Natchiar
- , Alexander G. Myasnikov
- & Bruno P. Klaholz
Genome organization around nuclear speckles drives mRNA splicing efficiency