Featured
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| Open AccessChromatin remodeling by Pol II primes efficient Pol III transcription
Transcription of RNA polymerase II is coupled with remodeling of chromatin. This study reports that transcription of RNA polymerase II is also required to prime and maintain nucleosome depletion at RNA polymerase III loci.
- Carlo Yague-Sanz
- , Valérie Migeot
- & Damien Hermand
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Article
| Open AccessTumour mutations in long noncoding RNAs enhance cell fitness
The role of mutations within long noncoding RNAs (lncRNAs) exons on tumour cell fitness remains to be explored. Here, the authors investigate the landscape of driver lncRNAs in primary and metastatic samples and validate the functional significance of single nucleotide variants in the NEAT1 oncogene in vitro and in vivo.
- Roberta Esposito
- , Andrés Lanzós
- & Rory Johnson
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| Open AccessSpatial distribution of three ARGONAUTEs regulates the anther phasiRNA pathway
Spatial and intracellular control of three Argonaute proteins is crucial for anther development in rice. Two, AGO1b and AGO1d, may carry 1st uracil–phasiRNAs as mobile signals from the somatic cell layers to the germ cells in the anther.
- Hinako Tamotsu
- , Koji Koizumi
- & Reina Komiya
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| Open AccessLIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways
LIS1 protein is important for brain development and stem cells’ survival. Here the authors show that LIS1 binds RNA and interact with RNA-binding proteins regulating the physical properties of mouse embryonic stem cells.
- Aditya Kshirsagar
- , Svetlana Maslov Doroshev
- & Orly Reiner
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| Open AccessIdentification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy
Circular RNAs are known to be linked to cancer regulation. Here, the authors identify a circular RNA signature associated with immune checkpoint response in melanoma.
- Yu Dong
- , Qian Gao
- & Youqiong Ye
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Article
| Open AccessLncRNA modulates Hippo-YAP signaling to reprogram iron metabolism
Iron metabolism dysregulation is associated with various diseases including cancer. Here, the authors show that one iron-triggered lncRNA LncRIM regulates cellular iron metabolism effectively by wiring up the Hippo-YAP signaling pathway and promotes breast cancer development.
- Xin-yu He
- , Xiao Fan
- & Aifu Lin
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Article
| Open AccessScreening of Drosophila microRNA-degradation sequences reveals Argonaute1 mRNA’s role in regulating miR-999
miRNAs typically bind to target mRNAs to induce their degradation but when base-pairing between miRNAs and the target RNAs are extended, miRNAs themselves can be degraded. Here, by employing AGO1-CLASH in Drosophila cells, the authors show that RNA sequence in AGO1 mRNA 3′UTR induces decay of miR-999.
- Peike Sheng
- , Lu Li
- & Mingyi Xie
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Article
| Open AccessBombyx Vasa sequesters transposon mRNAs in nuage via phase separation requiring RNA binding and self-association
Bombyx Vasa assembles Vasa bodies, the site of transposon silencing by Siwi and Ago3-piRISC formation. Here, the authors show Vasa sequesters transposon mRNAs in Vasa bodies via phase separation requiring RNA binding and self-association of Vasa.
- Hiroya Yamazaki
- , Yurika Namba
- & Mikiko C. Siomi
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Article
| Open AccessThe 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
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Article
| Open AccessPaternal methotrexate exposure affects sperm small RNA content and causes craniofacial defects in the offspring
Anti-folate drugs, such as methotrexate, have been largely prohibited for pregnant women because of the teratogenic effect on their descendant. Here, the authors report a intergenerational mechanism by why paternal methotrexate exposure causes craniofacial defects on their offspring.
- Nagif Alata Jimenez
- , Mauricio Castellano
- & Pablo H. Strobl-Mazzulla
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Article
| Open AccessPolynucleotide phosphorylase protects against renal tubular injury via blocking mt-dsRNA-PKR-eIF2α axis
Renal tubular atrophy is a hallmark of chronic kidney disease. The study by Zhu et al. reveals the protective role of tubular polynucleotide phosphorylase (PNPT1) against renal atrophy by blocking the leakage of mitochondrial dsRNAs into cytoplasm where they activate the PKReIF2α axis and terminate translation.
- Yujie Zhu
- , Mingchao Zhang
- & Ke Zen
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Article
| Open AccessIdentification of a physiologic vasculogenic fibroblast state to achieve tissue repair
Here, the authors report on the discovery of physiological vasculogenic fibroblasts capable of forming functional blood vessels. In vivo tissue reprogramming triggered by topical tissue nanotransfection (TNT) of a single anti-miR-200b oligonucleotide achieved therapeutic tissue vascularization.
- Durba Pal
- , Subhadip Ghatak
- & Chandan K. Sen
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Article
| Open AccessmcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs
Metabolic reprogramming plays vital roles in tumorigenesis. Here, Chen et al. reveal that mitochondria-encoded mcPGK1 drives the mitochondrial translocation of PGK1, promoting liver tumorigenesis and TIC self-renewal by switching energy production from OXPHOS to glycolysis.
- Zhenzhen Chen
- , Qiankun He
- & Pingping Zhu
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Article
| Open AccessLong non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response
Long noncoding RNA molecules are RNA transcripts long thought to remain untranslated. In this study, the authors demonstrate that certain lncRNA can be translated into peptides that are immunogenic to CD8+ T cells and promote anti-tumour responses when delivered as vaccine vectors in mice.
- Wojciech Barczak
- , Simon M. Carr
- & Nicholas B. La Thangue
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Article
| Open AccessDynamic interplay between non-coding enhancer transcription and gene activity in development
Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its function remains uncertain. Here the authors show that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription.
- Kota Hamamoto
- , Yusuke Umemura
- & Takashi Fukaya
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Article
| Open AccessAmniotes co-opt intrinsic genetic instability to protect germ-line genome integrity
Pachytene Piwi-interacting RNAs (piRNAs) expressed in mammalian germ lines are abundant, but their evolution and function are not fully understood. Here, the authors find that pachytene piRNA loci are hotspots of structural variation, which underlies rapid piRNA birth, divergence, and loss.
- Yu H. Sun
- , Hongxiao Cui
- & Xin Zhiguo Li
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Article
| Open AccessZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells
The metastability of stem cells requires a mechanism for actively blocking dedifferentiation to achieve successful differentiation. Here the authors show that ZBTB12 serves as a molecular barrier to dedifferentiation by repressing a primate-specific retrotransposon, HERVH.
- Dasol Han
- , Guojing Liu
- & Jiwon Jang
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Article
| Open AccessCircular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity
Pancreatic β-cell compensation is a major mechanism in delaying T2DM progression. Here, the authors show that circGlis3 levels are affected by QKI and FUS expression, and that increasing circGlis3 lengthens β-cell compensation via enhancing insulin secretion and reducing apoptosis.
- Yue Liu
- , Yue Yang
- & Liang Jin
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Article
| Open AccessAn RNA sponge controls quorum sensing dynamics and biofilm formation in Vibrio cholerae
Small regulatory RNAs (sRNAs) often act in concert with the RNA-chaperone Hfq to regulate the expression of multiple target transcripts in bacteria. Here, the authors identify Hfq-interacting sRNAs and their targets in the pathogen Vibrio cholerae, including an RNA sponge that binds and inactivates four sRNAs that modulate the quorum sensing pathway.
- Michaela Huber
- , Anne Lippegaus
- & Kai Papenfort
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Article
| Open AccessAltered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila
La proteins are conserved factors critical for the maturation of RNA polymerase III transcripts. In the ciliate T. thermophila and related alveolates, La proteins have a novel domain arrangement and are linked to a distinct pre-tRNA processing pathway.
- Kyra Kerkhofs
- , Jyoti Garg
- & Mark A. Bayfield
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Article
| Open AccesscircCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment
Circular RNAs can contribute to tumour progression. Here the authors show that two circular RNAs, circCsnk1g3 and circAnkib1 promote sarcoma growth by controlling the expression of interferon related genes and pro-inflammatory factors in sarcoma cells
- Roberta Piras
- , Emily Y. Ko
- & Jlenia Guarnerio
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Article
| Open Access2′–5′ oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability
Maintaining optimal eNOS levels is important during cardiovascular events, although little is known regarding the mechanism of eNOS protection. Here, the authors show a regulatory role of endothelial OASL1 in maintaining eNOS mRNA stability and vascular biology under atheroprone conditions.
- Tae Kyeong Kim
- , Sejin Jeon
- & Goo Taeg Oh
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Article
| Open AccessHIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex
Using a composite bioinformatics approach, the DNA:DNA:RNA triplex-forming lncRNAs HIF1α-AS1 was identified in human endothelial cells which recruits an epigenetic silencing complex to limit expression of triplex target genes.
- Matthias S. Leisegang
- , Jasleen Kaur Bains
- & Ralf P. Brandes
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Article
| Open AccessXPF activates break-induced telomere synthesis
Here the authors show TERRA R-loops recruit the endonuclease XPF to telomeres, leading to DNA double-strand breaks to activate break-induced telomere synthesis at telomeres that utilize the alternative lengthening of telomeres (ALT) pathway to extend their telomeres independent of telomerase.
- Chia-Yu Guh
- , Hong-Jhih Shen
- & Hsueh-Ping Catherine Chu
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Article
| Open AccessExportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs
This study identifies the evolutionarily conserved Exportin 4 as an essential regulator in the nuclear export of circRNAs. Defective circRNA export results in R-loop formation and DNA damage in cells, as well as testis and neurological defects in mice.
- Liang Chen
- , Yucong Wang
- & Ge Shan
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Article
| Open AccessMicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis
The hypothalamus controls systemic energy homeostasis. Here, the authors show that loss of microRNA-7 in hypothalamic neurons causes obesity, increased growth and endocrine dysfunction in mice, and report genetic evidence that links microRNA-7 to height and adiposity in humans.
- Mary P. LaPierre
- , Katherine Lawler
- & Markus Stoffel
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Article
| Open AccessGLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance
Phase separated, membrane-less germ granules preserve fertility and cellular function in animal germ cells. Here the authors show that loss of germ granules impacts piRNA pathway fidelity in the recognition of self and non-self nucleic acids.
- Wenjun Chen
- , Jordan S. Brown
- & Heng-Chi Lee
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Article
| Open AccessTENT2, 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
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Article
| Open AccessStructural and mechanistic basis for recognition of alternative tRNA precursor substrates by bacterial ribonuclease P
Ribonuclease P efficiently processes all tRNA precursors despite sequence variation at the site of cleavage. Here, authors use high-throughput enzymology and cryoEM to reveal conformational changes that drive recognition by bacterial RNase P.
- Jiaqiang Zhu
- , Wei Huang
- & Michael E. Harris
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Article
| Open AccessHnRNPK maintains single strand RNA through controlling double-strand RNA in mammalian cells
Using fibroblast growth factor 2 (FGF-2) induced sense and antisense transcripts IER3 and IER3-AS1 as a model system, authors highlight the role of HnRNPK in regulating double strand RNA formation in the loci with overlapping transcripts.
- Sagar Mahale
- , Meenakshi Setia
- & Meena Kanduri
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Article
| Open AccessDicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice
Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene.
- Juan Roa
- , Miguel Ruiz-Cruz
- & Manuel Tena-Sempere
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Article
| Open AccessXist exerts gene-specific silencing during XCI maintenance and impacts lineage-specific cell differentiation and proliferation during hematopoiesis
Here the authors investigate the functional relevance of X-chromosome inactivation (XCI) regulator Xist in hematopoiesis. They find that Xist loss leads to changes in the ratio of hematopoietic progenitor cells and results in chromatin accessibility and transcriptional upregulation on the inactive X chromosome, including XCI escape genes known to be associated with cell cycle and immune response.
- Tianqi Yang
- , Jianhong Ou
- & Eda Yildirim
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Article
| Open AccessThe HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors
Long non-coding RNAs (lncRNAs) can contribute to cancers that are driven by Sonic hedgehog (SHH) signaling. Here the authors report that lncRNA HHIP-AS1 stabilises the mRNA of dynein complex 1, thereby, promoting the pro-mitotic effects of SHH-driven tumors.
- Jasmin Bartl
- , Marco Zanini
- & Marc Remke
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Article
| Open AccessPervasive translation of circular RNAs driven by short IRES-like elements
Unbiased screen of random sequences identified many short IRES-like elements to drive circular RNA translation and hundreds of rolling circle translation events, suggesting a pervasive cap-independent translation in human transcriptome.
- Xiaojuan Fan
- , Yun Yang
- & Zefeng Wang
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Article
| Open AccessMicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake
The microRNA miR-21 is induced in the islets of patients with glucose intolerance and diabetic mice. Here the authors report that deletion of miR-21 in pancreatic β-cells impairs glucose-stimulated insulin secretion via reduced glucose uptake, while a miR-21 agomir reduces blood glucose leves in diabetic male mice.
- Ruiling Liu
- , Cuilian Liu
- & Qingguo Ruan
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Article
| Open AccessControl of CRK-RAC1 activity by the miR-1/206/133 miRNA family is essential for neuromuscular junction function
The miR-1/133/206 gene family codes for the most abundant microRNAs in striated muscles. Here, Klockner et al show that inactivation of all family members in skeletal muscle prevents formation of normal neuromuscular junctions due to increased expression of the adaptor protein CRK.
- Ina Klockner
- , Christian Schutt
- & Thomas Braun
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Article
| Open AccessA cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
RNA polymerase III changes its subunit composition during mammalian development. Here the authors report that loss of subunit POLR3G, which re-emerges in cancer, promotes expression of small NF90-associated RNA (snaR-A), a noncoding RNA implicated in cell proliferation and metastasis.
- Kevin Van Bortle
- , David P. Marciano
- & Michael P. Snyder
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Article
| Open AccessThe long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase
Adipocyte-expressed long non-coding RNAs (lncRNAs) have been shown to regulate the transcription of genes involved in lipid metabolism. Here the authors describe a human adipocyte-specific lncRNA, ADIPINT, which regulates lipid metabolism in white adipocytes in part through its interaction with the metabolic enzyme pyruvate carboxylase.
- Alastair G. Kerr
- , Zuoneng Wang
- & Hui Gao
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Article
| Open AccessThe 3′ Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies’ association with histone locus bodies
Transcription termination is generally accompanied by the 3′-end processing of transcripts. Here the authors demonstrate a role for Mediator in transcript end site proximal pausing of replication-dependent histone genes.
- Hidefumi Suzuki
- , Ryota Abe
- & Hidehisa Takahashi
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Article
| Open AccessSmall extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1
The pathological mechanisms that lead to Ossification of the posterior longitudinal ligament (OPLL) are unclear. Here, the authors show that OPLL ligament cells produce small extracellular vesicles that induce ossification via miR-320e/TAK1 signaling in mice and human posterior longitudinal ligament cells.
- Chen Xu
- , Zicheng Zhang
- & Wen Yuan
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Article
| Open AccessContext-specific effects of sequence elements on subcellular localization of linear and circular RNAs
Ron and Ulitsky found using massively parallel assays that the effects of short RNA sequences on the subcellular localization of their host RNAs are strongly dependent on the host RNA form, linear or circular, and spliced or unspliced.
- Maya Ron
- & Igor Ulitsky
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Article
| Open AccessEnhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF
Enhancer RNAs (eRNAs) can stimulate gene transcription through various mechanisms. Here, the authors identify the molecular features within eRNAs that are critical for their action in facilitating RNA Polymerase II release from the paused state.
- Vladyslava Gorbovytska
- , Seung-Kyoon Kim
- & Claus-D. Kuhn
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Article
| Open AccessDual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis
Osteoarthritic (OA) is characterized by progressive destruction of joint cartilage. Here, the authors show that microRNA-17 plays a dual role in maintaining cartilage homeostasis and in the prevention of osteoarthritis, by targeting hypoxia-inducible factor-1α as well as multiple matrix-degrading enzymes.
- Yun Zhang
- , Shuaijun Li
- & Lei Cui
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Article
| Open AccessDiversity of bacterial small RNAs drives competitive strategies for a mutual chaperone
Bacterial sRNAs compete for limited copies of an RNA chaperone. Here, real-time single-molecule imaging shows that pairwise interactions of sRNAs with Hfq determine if the sRNAs are actively exchanged or stably coexist on the shared protein.
- Jorjethe Roca
- , Andrew Santiago-Frangos
- & Sarah A. Woodson
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Article
| Open AccessTRMT6/61A-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
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Article
| Open AccessAn evolutionarily conserved stop codon enrichment at the 5′ ends of mammalian piRNAs
Piwi-interacting RNAs are small RNAs produced by processing of long precursor transcripts. Here the authors report that precursor cleavage typically occurs at positions corresponding to stop codons and that this pattern is conserved across mammals.
- Susanne Bornelöv
- , Benjamin Czech
- & Gregory J. Hannon
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Article
| Open AccessSecondary structure RNA elements control the cleavage activity of DICER
MicroRNA precursors are cleaved by DICER to generate mature microRNAs in the cytoplasm. Here the authors employ high-throughput analysis of DICER cleavage activity and identify RNA secondary elements in precursor miRNAs and shRNAs, including a single nucleotide bulge, which govern its cleavage efficiency and accuracy.
- Trung Duc Nguyen
- , Tam Anh Trinh
- & Tuan Anh Nguyen
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Article
| Open AccessStructural basis of R-loop recognition by the S9.6 monoclonal antibody
The S9.6 monoclonal antibody is widely used to map R-loops genome wide. Here, Bou-Nader et al., define the nucleic acid-binding specificity of S9.6 and report its crystal structures free and bound to a hybrid, which reveal the asymmetric recognition of the RNA and DNA strands and its A-form conformation.
- Charles Bou-Nader
- , Ankur Bothra
- & Jinwei Zhang
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Article
| Open AccessSiwi cooperates with Par-1 kinase to resolve the autoinhibitory effect of Papi for Siwi-piRISC biogenesis
Siwi-piRISC protects the germline genome from DNA damage caused by selfish movement of transposons by suppressing their expression. Here, the authors show how molecularly Papi, which plays an important role in the production of Siwi-piRISC, cooperates with Par-1 kinase to ensure the accumulation of Siwi-piRISC in germ cells.
- Hiromi Yamada
- , Kazumichi M. Nishida
- & Mikiko C. Siomi