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Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1
Endothelial dysfunction has been shown to occur in HFpEF and we know that statins can target endothelial dysfunction by inhibiting miR-133a. Here the authors show that statins improve diastolic dysfunction in HFpEF by increasing the levels of a circRNA which, in turns, binds to miR-133a modulating its downstream targets.
- Bin Li
- , Wen-Wu Bai
- & Shuang-Xi Wang
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| Open Access
A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis
By tracing promoter expression in lineage-mapped single cells, Xu et al. present a whole-body cartography of microRNA transcriptional activities during C. elegans embryogenesis and demonstrate its broad utility in multifaceted functional analyses.
- Weina Xu
- , Jinyi Liu
- & Zhuo Du
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Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity
Long noncoding RNAs (lncRNAs) function in many processes yet their participation in learning is largely unknown. Here, we identify and characterize the lncRNA SLAMR, which is recruited to stimulated synapses to mediate structural plasticity during experience and fear memory consolidation.
- Isabel Espadas
- , Jenna L. Wingfield
- & Sathyanarayanan Puthanveettil
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| Open Access
NAP-seq reveals multiple classes of structured noncoding RNAs with regulatory functions
The genome-wide prevalence, mechanism and function of noncapped RNAs (napRNAs) are currently poorly understood. Here, the authors develop a method called NAP-seq, to globally profile the full-length sequences of napRNAs, revealing several classes of structured noncoding RNAs.
- Shurong Liu
- , Junhong Huang
- & Jianhua Yang
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Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis
MALAT1 is a long non-coding RNA that is known to suppress breast cancer lung metastasis. Here the authors show that MALAT1 is downregulated during osteoclastogenesis and its loss derepresses Tead3, promoting Nfatc1-mediated osteoclast differentiation and enhancing bone metastasis.
- Yang Zhao
- , Jingyuan Ning
- & Li Ma
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Article
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The spliceosome-associated protein CWC15 promotes miRNA biogenesis in Arabidopsis
CWC15 is a spliceosome-associated protein in Arabidopsis. Here the authors reports a multifaceted role of CWC15 in promoting microRNA (miRNA) biogenesis by binding to miRNA promoters and interacting with microprocessor components.
- Bangjun Zhou
- , Huihui Yu
- & Bin Yu
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piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis
piRNA processing factors and piRNA/PIWI complex are found in intermitochondrial cement (IMC) and chromatoid body (CB). Here, the authors show that piRNA loading orchestrates MIWI translocation from the IMC to CB, demonstrating its crucial role in spermatogenesis.
- Huan Wei
- , Jie Gao
- & Mo-Fang Liu
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RNA compaction and iterative scanning for small RNA targets by the Hfq chaperone
Small RNAs (sRNAs) turn bacterial genes on or off by base pairing with mRNAs. Here the authors employ single molecule fluorescence to show how sRNAs and their chaperone Hfq quickly locate the proper target by repeatedly scanning an mRNA until a stable match is found.
- Ewelina M. Małecka
- & Sarah A. Woodson
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Article
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A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study
Alternative polyadenylation (APA) can play a key role in cancer initiation and progression. Here, the authors conducted a comprehensive pan-cancer APA TWAS analysis and discovered a distinct class of APA-mediated cancer susceptibility genes across 22 cancer types.
- Hui Chen
- , Zeyang Wang
- & Lei Li
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Interplay between coding and non-coding regulation drives the Arabidopsis seed-to-seedling transition
Seed germination in plants is a tightly controlled process relying on translation of stored RNAs. Here, Tremblay et al. show that nascent transcriptome and epigenome reprogramming are detected from initial stages of germination.
- Benjamin J. M. Tremblay
- , Cristina P. Santini
- & Julia I. Qüesta
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| Open Access
Decryption of sequence, structure, and functional features of SINE repeat elements in SINEUP non-coding RNA-mediated post-transcriptional gene regulation
Here the authors elucidate structure-function relationships of SINEUPs, antisense long non-coding RNAs that through SINE repeat elements positively regulate protein translation of mRNAs they pair with. SINEUP’s functional domains do not share common ancestors.
- Harshita Sharma
- , Matthew N. Z. Valentine
- & Piero Carninci
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Nutrient-dependent regulation of a stable intron modulates germline mitochondrial quality control
The quality of germline mitochondria is essential for producing healthy oocytes. Here, Ng, Chan and Pek report a stable intron that modulates germline mitochondrial quality control during fasting, heat stress and aging.
- Annabel Qi En Ng
- , Seow Neng Chan
- & Jun Wei Pek
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Regulation of TRI5 expression and deoxynivalenol biosynthesis by a long non-coding RNA in Fusarium graminearum
The fungus Fusarium graminearum produces a toxin, deoxynivalenol (DON), that can be found in cereal grains and processed food or feed. Here, Huang et al. study the regulation of DON biosynthesis and show that transcription factors TRI6 and TRI10 regulate each other’s expression and that of a long non-coding RNA which, in turn, downregulates a DON biosynthesis gene.
- Panpan Huang
- , Xiao Yu
- & Cong Jiang
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Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans
Wang et al. profile age-dependent miRNAomic changes in worm tissues and extracellular vesicles (EVs). They show that ageing controls miRNAs in a tissue-specific manner and their findings further suggest a complex EV-mediated miRNA trafficking network across tissues.
- Xueqing Wang
- , Quanlong Jiang
- & Yidong Shen
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The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors
Replication stress represents a major threat to genome integrity of normal and cancer cells. Here, the authors find that the long non-coding RNA lncREST affects the replication stress response through interaction with nucleolin. This interaction bridges the recruitment of replication factors to stressed chromatin.
- Luisa Statello
- , José Miguel Fernandez-Justel
- & Maite Huarte
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HRDE-2 drives small RNA specificity for the nuclear Argonaute protein HRDE-1
Argonaute proteins are loaded with small RNAs to confer target RNA specificity and proper gene silencing. Here, the authors establish that HRDE-2 recruits the unloaded nuclear Argonaute HRDE-1 to germ granules to facilitate correct small RNA loading.
- Shihui Chen
- & Carolyn M. Phillips
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Article
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Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging
Events that cause neurons to die in Alzheimer’s disease (AD) are poorly understood. Here, the authors provide evidence for a role of RNA interference in AD. Short RNAs causing neurotoxicity and DNA damage are seen in AD and aged brains, and are counteracted by nontoxic RNAs.
- Bidur Paudel
- , Si-Yeon Jeong
- & Marcus E. Peter
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Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system
Short prokaryotic Argonaute and Sir2 proteins function as an antivirus system. Here the authors describe structures of SPARSA (a heterodimer of Sir2-APAZ and prokaryotic Argonaute) with and without template DNA and guide RNA, providing structural basis of its assembly and activation by the recognition of the invading virus.
- Xiangkai Zhen
- , Xiaolong Xu
- & Songying Ouyang
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The long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis
Although patients with rheumatoid arthritis (RA) usually exhibit symmetrical joint involvement, some can develop alternative patterns of arthritis, often translating into differences in responsiveness to treatment. In this study, the authors propose that the long-noncoding RNA, HOTAIR, might contribute to these differences.
- Muriel Elhai
- , Raphael Micheroli
- & Caroline Ospelt
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LncRNA MIR200CHG inhibits EMT in gastric cancer by stabilizing miR-200c from target-directed miRNA degradation
The roles of long non-coding RNAs (lncRNAs) in different subtypes of gastric cancer (GC) remain to be characterized. Here, the authors identify lncRNA MIR200CHG as a master regulator of Microsatellite stable (MSS)/epithelial-mesenchymal transition (EMT) GC subtype, which inhibits EMT and metastasis by stabilizing miR-200c.
- Yixiao Zhu
- , Chengmei Huang
- & Xin Wang
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Excess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid–liquid phase separation implicated in myopathy
The prion protein PrPC is known to play a role in skeletal muscle development and physiology, including in myopathy. Here, the authors report that excess PrPC binds microRNAs that enhance its aggregation, which inhibits autophagy in muscle cells.
- Jing Tao
- , Yanping Zeng
- & Yi Liang
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| Open Access
In vivo RNA interactome profiling reveals 3’UTR-processed small RNA targeting a central regulatory hub
Here the authors report a new approach to profile RNA-RNA interactions in live bacterial cells. The charted RNA interaction networks unveil a key mRNA regulatory hub targeted by twelve small RNAs, including a novel RNA involved in fatty acid metabolism.
- Fang Liu
- , Ziying Chen
- & Yanjie Chao
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MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease
Cisplatin, a chemotherapy drug, can cause long-lasting kidney injury. The authors explore miRNA:mRNA interactions in cisplatin-injured kidneys and find that such a cisplatin inducible miRNA as miR-429-3p suppresses the catabolism of branched-chain amino acids, leading to stimulation of ferroptotic cell death.
- Hisakatsu Sone
- , Tae Jin Lee
- & Sang-Ho Kwon
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| Open Access
Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
Synaptic activity controls the extinction of conditioned fear. Here the authors discovered a new way that the brain controls memories of fear: a long noncoding RNA called Gas5 that coordinates the activity of RNA granules in the synaptic compartment.
- Wei-Siang Liau
- , Qiongyi Zhao
- & Timothy W. Bredy
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| Open Access
Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing
Regulatory miRNAs have significant therapeutic potential. Here the authors developed a screen to identify small molecule drugs that modulate miRNome profiles in human neurons and validated cardiac glycosides as inducers of the neuroprotective miR-132.
- Lien D. Nguyen
- , Zhiyun Wei
- & Anna M. Krichevsky
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| Open Access
LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
Long noncoding RNAs (lncRNAs) may contribute to cancer progression. Here the authors show that LncRNA INHEG modulates rRNA 2’-O-methylation and facilitates mRNA translation to promote glioma stem cell renewal and growth.
- Lihui Liu
- , Ziyang Liu
- & Runsheng Chen
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| Open Access
Unistrand piRNA clusters are an evolutionarily conserved mechanism to suppress endogenous retroviruses across the Drosophila genus
To control transposable elements, fruit flies rely on distinct genomic regions called piRNA clusters. Here, new piRNA clusters were identified across diverse Drosophila species, displaying a conserved and specialised role in the control of endogenous retroviruses in ovarian somatic cells.
- Jasper van Lopik
- , Azad Alizada
- & Benjamin Czech Nicholson
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Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs
ALT cells use an alternative lengthening mechanism of telomeres and bear telomeric DNA damage with increased levels of damage-induced long non-coding RNA. Here the AUs show that antisense oligonucleotides (ASO) targeting such RNAs can induce ALT cancer cells selective cell death.
- Ilaria Rosso
- , Corey Jones-Weinert
- & Fabrizio d’Adda di Fagagna
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The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury in murine males
LncRNAs take part in fine-tuning gene regulatory networks in development, homeostasis, and disease settings. Here, the authors show that the lncRNA Sweetheart has an important role in cardiomyocytes after myocardial injury to act together with NKX2-5 in adapting gene programs after myocardial stress.
- Sandra Rogala
- , Tamer Ali
- & Phillip Grote
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A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability
TGFbeta is known to promote cancer metastasis through the promotion of epithelial-mesenchymal transition (EMT). Here, the authors demonstrate that a TGFbeta induced circular RNA (circITGB6) promotes colorectal cancer metastasis via activation of the m6A reader protein, IGF2BP3, resulting in stabilization of an EMT-promoting gene, PDPN.
- Ke Li
- , Jiawei Guo
- & Yong Peng
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| Open Access
Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions
Many types of RNAs are associated with chromatin. Here the authors identify chromatin-bound RNAs and their binding sites in human embryonic stem cells suggesting that most chromatin-associated RNAs act proximal to their encoding loci and single RNAs are unlikely to alter gene expression.
- Charles Limouse
- , Owen K. Smith
- & Aaron F. Straight
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C. elegans germ granules sculpt both germline and somatic RNAome
Germ granules are membraneless organelles that act as organizing centers for small RNA biogenesis during germline development. Here they show the LOTUS domain protein eggd-1 organizes germ granules, and reveal a germ line-to-soma communication pathway activated upon perturbation of germ granules.
- Ian F. Price
- , Jillian A. Wagner
- & Wen Tang
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Epigenomic analysis of formalin-fixed paraffin-embedded samples by CUT&Tag
Conducting epigenomic studies on FFPE samples is traditionally challenging due to chromatin damage caused due to exposure to formaldehyde. Here, the authors show that an optimisation of their previous CUTAC method allows the production of high-resolution maps of regulatory elements from FFPE samples.
- Steven Henikoff
- , Jorja G. Henikoff
- & Eric C. Holland
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Telomerase RNA-based aptamers restore defective myelopoiesis in congenital neutropenic syndromes
The RNA component telomerase (TERC) has a critical non-canonical role in the formation of the myeloid lineage. Here, the authors show aptamers that mimic the behaviour of the entire TERC molecule in myelopoiesis activation.
- Elena Martínez-Balsalobre
- , Jesús García-Castillo
- & María L. Cayuela
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Discovery of the major 15–30 nt mammalian small RNAs, their biogenesis and function
The authors uncover the major 15-30 nt mouse and human small RNAs (sRNAs), which mainly end with 2’,3’-cyclic phosphate, and show that many of these sRNAs can be generated by Angiogenin or RNase 4 and function in Ago2 complex as miRNAs.
- Hejin Lai
- , Ning Feng
- & Qiwei Zhai
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| Open Access
A linear and circular dual-conformation noncoding RNA involved in oxidative stress tolerance in Bacillus altitudinis
The presence and/or biological functionality of circular RNAs in bacteria are unclear. Here, the authors identify a dual-conformation (linear and circular) noncoding RNA that promotes tolerance to oxidative stress in Bacillus altitutidinis, and provide evidence for the existence of other circular RNAs in diverse bacterial species.
- Ting-Ting He
- , Yun-Fan Xu
- & Hai-Yan Wang
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| Open Access
Direct observation of tRNA-chaperoned folding of a dynamic mRNA ensemble
T-box riboswitch RNAs directly bind to specific tRNA and regulate the transcription or translation of downstream genes in bacteria. Using single-molecule FRET and ensemble biophysical analyses, here the authors uncover a Venus flytrap-like mechanism where tRNA binding to a T-box riboswitch mRNA triggers its rapid domain closure.
- Krishna C. Suddala
- , Janghyun Yoo
- & Jinwei Zhang
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| Open Access
The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters
The role of PIWI proteins in mammalian reproduction remains poorly understood. Here, using golden hamsters, the authors establish expression profiles for all four PIWIs during gametogenesis and characterize their associated reproductive defects.
- Xiaolong Lv
- , Wen Xiao
- & Ligang Wu
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Article
| Open Access
TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation
Proliferation of cancer cells leads to replication stress through incompletely understood mechanisms. Here, the authors show that the long noncoding RNA TUG1 resolves R-loops and reduces replication stress in cancer cells.
- Miho M. Suzuki
- , Kenta Iijima
- & Yutaka Kondo
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| Open Access
LINE-1 regulates cortical development by acting as long non-coding RNAs
Here the authors reveal that by acting as non-coding RNAs, L1s are bound by PRC2 and inhibit its activity on genes crucial for regulating proliferation and differentiation in neural progenitor cells.
- Damiano Mangoni
- , Alessandro Simi
- & Stefano Gustincich
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| Open Access
Mechanism of U6 snRNA oligouridylation by human TUT1
U6 snRNA plays a catalytic role in pre-mRNA splicing. Here the authors report the structure of human terminal uridyltransferase, TUT1, complexed with U6 snRNA revealing the mechanism of specific uridylation of U6 snRNA by TUT1.
- Seisuke Yamashita
- & Kozo Tomita
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Article
| Open Access
Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage
Macrophages are increasingly recognized as key drivers of lung damage in acute pneumonia including COVID-19. Here, the authors report on a first-in-class, inhalable, carbohydrate-coupled microRNA-inhibitor for selective targeting of macrophages and that prevents pulmonary hyperinflammation.
- Christina Beck
- , Deepak Ramanujam
- & Stefan Engelhardt
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Article
| Open Access
ORC1 binds to cis-transcribed RNAs for efficient activation of replication origins
Here the authors describe that the human origin recognition complex subunit 1 (ORC1) binds to RNAs transcribed from genes with origins of replication at their TSS impacting origin activation.
- Aina Maria Mas
- , Enrique Goñi
- & Maite Huarte
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Article
| Open Access
An RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis
Here the authors found an RNA modifying enzyme that serves as a molecular switch, directly relaying the sensing of reactive oxygen species to chemical modifications in rRNA and tRNA for increasing stress response proteins in the proteome.
- Wei Lin Lee
- , Ameya Sinha
- & Peter Dedon
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Article
| Open Access
The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation
The transcription factor ΔNp63 is a master regulator of epithelial development and integrity of stratified epithelial tissues. Here, the authors unveiled the lncRNA NEAT1 as an additional player of the highly complex regulatory network by which ΔNp63 controls epidermal homeostasis.
- Claudia Fierro
- , Veronica Gatti
- & Angelo Peschiaroli
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| Open Access
Chromatin 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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| Open Access
Tumour 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 Access
Spatial 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 Access
LIS1 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
An Intricate Network Involving the Argonaute ALG-1 Modulates Organismal Resistance to Oxidative Stress