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Sample sequencing of vascular plants demonstrates widespread conservation and divergence of microRNAs
Small RNAs and microRNAs are important regulators of gene expression. In this study, Chávez Montes et al.examine these molecules in 34 plant species, and explore the correlations between abundance, conservation and variability of microRNA sequences across all of the species studied.
- Ricardo A. Chávez Montes
- , de Fátima Flor Rosas-Cárdenas
- & Stefan de Folter
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| Open AccessLin28a regulates neuronal differentiation and controls miR-9 production
microRNAs regulate gene expression and control cell fate and differentiation processes. In this work, Nowak et al. reveal that brain-specific miR-9 is under post-transcriptional control and that the pre-miR-9 binding protein Lin28a decreases the levels of mature miR-9 during retinoic acid-mediated neuronal differentiation.
- Jakub S. Nowak
- , Nila Roy Choudhury
- & Gracjan Michlewski
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CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation
The prohibitin complex promotes cell survival by regulating mitochondrial morphogenesis. Wang et al.identify a long non-coding RNA that regulates this complex in cardiomyocytes by acting as a sponge to downregulate a prohibitin-targetting miRNA, protecting cells from apoptosis in anoxic conditions.
- Kun Wang
- , Bo Long
- & Pei-Feng Li
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2′-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity
Short interfering siRNAs—siRNAs—have therapeutic potential in the treatment of disease; however, their delivery to target tissues is difficult. Here, Wu et al. chemically modify siRNAs and show that this improves loading into the siRNA silencing machinery and thus efficacy in eliminating cancer cells in mice.
- Sherry Y. Wu
- , Xianbin Yang
- & Anil K. Sood
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Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex
Amyloid precursor protein (APP) is implicated in neurogenesis in the mammalian embryonic brain. Here, Zhang et al. show that APP suppresses brain-specific miRNA-574-5p to regulate the balance between proliferation and differentiation of neural progenitor cells in the developing mouse cerebral cortex.
- Wei Zhang
- , Selvaratnam Thevapriya
- & Li Zeng
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HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells
Lipoproteins such as HDL can bind and transport microRNAs throughout the body. Here the authors provide a new mechanism contributing to the anti-inflammatory effects of HDL by which HDL-associated miR-223 is transferred to endothelial cells, where it inhibits expression of the adhesion molecule ICAM-1.
- Fatiha Tabet
- , Kasey C. Vickers
- & Kerry-Anne Rye
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Bio-barcode gel assay for microRNA
MicroRNA has been identified to play a role in cancer development, thus its detection at low concentrations would be a highly beneficial diagnostic tool. Here, the authors develop a gel-based bio-barcode assay for microRNA detection using DNA-modified gold nanoparticles, with aM limits of detection.
- Hyojin Lee
- , Jeong-Eun Park
- & Jwa-Min Nam
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miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression
microRNAs inhibit mRNA translation and are implicated in modulating synaptic plasticity. Here, Hu et al.show that miR-191 and miR-135 regulate the expression of tropomodulin 2 and complexin-1/2 to produce dendritic spine remodelling, which is associated with synaptic long-term depression.
- Zhonghua Hu
- , Danni Yu
- & Zheng Li
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miR828 and miR858 regulate homoeologous MYB2 gene functions in Arabidopsis trichome and cotton fibre development
Tetraploid cotton contains two homoeologous genes GhMYB2A and GhMYB2D but their regulation is unclear. Here, GhMYB2D is shown to accumulate to higher levels than GhMYB2Aduring fibre initiation, and is a target of two microRNAs, generating ta-siRNAs, suggesting a role for microRNAs in the divergence of duplicate genes and fibre trait.
- Xueying Guan
- , Mingxiong Pang
- & Z. Jeffrey Chen
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| Open AccessThe pseudogene TUSC2P promotes TUSC2 function by binding multiple microRNAs
Non-coding RNAs have recently emerged as crucial regulators of gene expression. Here Rutnam et al.identify a pseudogene complementary to the 3′-UTR of the TUSC2 tumour suppressor that regulates TUSC2 levels by acting as a decoy for endogenous microRNAs and thereby inhibits tumorigenesis.
- Zina Jeyapalan Rutnam
- , William W. Du
- & Burton B. Yang
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| Open AccessmicroRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial–mesenchymal transition
Ovarian cancer is often diagnosed at a late stage when metastasis has already occurred. In this study, Parikh et al.show that mir-181a is involved in mediating the epithelial-to-mesenchymal transition in ovarian cancer, leading to activation of the TGF-β signalling pathway and metastasis.
- Aditya Parikh
- , Christine Lee
- & Analisa DiFeo
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| Open AccessSumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs
Cells secrete micro-RNAs by packaging them into exosomes; however, the mechanisms by which this packaging occurs are unclear. Here, the authors identify a sequence motif that confers exosomal targeting to micro-RNAs and identify a ribonucleoprotein complex that plays a role in this process.
- Carolina Villarroya-Beltri
- , Cristina Gutiérrez-Vázquez
- & Francisco Sánchez-Madrid
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The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis
Gene expression in the vascular endothelium is sensitive to shear forces exerted by the circulation. Here the authors identify miR-712 as a mechanosensitive microRNA expressed in endothelial cells and show that miR-712 inhibits pro-atherogenic processes by downregulating tissue inhibitor of metalloproteinase 3.
- Dong Ju Son
- , Sandeep Kumar
- & Hanjoong Jo
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Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination
The long non-coding RNA HOTAIR acts as a scaffold to bring together chromatin silencing complexes in the nucleus. Here, the authors show that HOTAIRalso serves as a scaffold between E3 ubiquitin ligases and their substrates and thereby enhances their ubiquitination.
- Je-Hyun Yoon
- , Kotb Abdelmohsen
- & Myriam Gorospe
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| Open AccessmiRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1
Several microRNAs have been implicated in the differentiation of immune cells. Here the authors analyse the global microRNA expression profiles of mouse haematopoietic stem cells and different stages of dendritic cell development and identify Notch1 as a target of miR-30b in regulatory dendritic cells.
- Xiaoping Su
- , Cheng Qian
- & Xuetao Cao
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| Open AccessMicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice
The micro-RNA miR-33 is encoded by an intron of the gene encoding sterol regulatory-binding protein 2 (SREBP-2) and controls cholesterol homoeostasis. Here, Horie et al.identify SREBP-1 as a target of miR-33 and show that deletion of miR-33 promotes diet-induced obesity and liver steatosis in mice.
- Takahiro Horie
- , Tomohiro Nishino
- & Koh Ono
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Cyclin D1 induction of Dicer governs microRNA processing and expression in breast cancer
Whether microRNA processing mediated by Dicer is regulated in a cell-cycle-dependent manner is unknown. Here, Chen et al.show that Cyclin D1, which is important in the control of the cell cycle, regulates the expression of Dicer, and that Cyclin D1 and Dicer expression levels correlate in breast cancer.
- Zuoren Yu
- , Liping Wang
- & Richard G. Pestell
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miR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos
The microRNAs miR-1 and miR-206 have identical seed sequences and have been reported to regulate angiogenesis in zebrafish by repressing VegfAa expression. Here, Lin et al.describe opposing roles of the two microRNAs in regulating VegfAa expression and therefore angiogenesis in zebrafish.
- Cheng-Yung Lin
- , Hung-Chieh Lee
- & Huai-Jen Tsai
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| Open AccessIdentification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif
AGO-CLIP permits the identification of miRNA target genes. Here, Hamilton et al. compile publicly available AGO-CLIP data and combine this information with miRNA analysis from The Cancer Genome Atlas, permitting the identification of an oncogenic miRNA superfamily that targets tumour suppressor genes.
- Mark P. Hamilton
- , Kimal Rajapakshe
- & Sean E. McGuire
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miRNAs confer phenotypic robustness to gene networks by suppressing biological noise
MicroRNAs are thought to confer robustness to biological processes, but clear experimental evidence is still needed. Here, Siciliano et al. construct a toggle-switch in mammalian cells to show that microRNAs buffer fluctuations in protein levels, thereby providing phenotypic robustness to gene regulatory networks.
- Velia Siciliano
- , Immacolata Garzilli
- & Diego di Bernardo
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Tumour angiogenesis regulation by the miR-200 family
The microRNA-200 family members have a role in regulating tumour angiogenesis but the underlying mechanism is unclear. In this study, Pecot et al.demonstrate that miR-200 affects angiogenesis by altering endothelial and cancer cell cytokine secretion.
- Chad V. Pecot
- , Rajesha Rupaimoole
- & Anil K. Sood
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The effects of carbon dioxide and temperature on microRNA expression in Arabidopsis development
An increase in the concentration of atmospheric carbon dioxide and warmer temperatures can alter plant growth and development. Here the authors show that these conditions can also elicit significant changes in microRNAs expression, including some which might induce early flowering in Arabidopsis.
- Patrick May
- , Will Liao
- & Qiong A. Liu
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Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing
MicroRNAs are known to be transcribed by RNA polymerase II. The authors show that microRNA promoters driven by TATA-box or NF-κB have increased rates of transcription re-initiation, which leads to local crowding of RNA polymerase II and lower efficiency of microRNA synthesis.
- Nadav Marbach-Bar
- , Amitai Ben-Noon
- & Rivka Dikstein
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| Open AccessHaemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21
microRNAs rapidly regulate gene expression and are implicated in cardiogenesis and angiogenesis. Banjo and colleagues show that the microRNA mir-21 is activated by the physical forces generated by blood flow, and that this regulates the development of heart valves in zebrafish.
- Toshihiro Banjo
- , Janin Grajcarek
- & Toshihiko Ogura
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MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1
Lung cancers have a high potential to become metastatic, which is a major cause of treatment failure. Here, the authors identify a microRNA that is upregulated in non-small-cell lung cancer and is associated with Hippo pathway modulation metastasis and poor clinical outcome.
- Ching-Wen Lin
- , Yih-Leong Chang
- & Pan-Chyr Yang
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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9
Microglia are specialized immune cells in the brain. Here Åkerblom and colleagues use a microRNA-9-regulated lentiviral vector for the targeted genetic modification of microglia in the rodent brain, presenting a tool that may facilitate functional studies of resident microglia.
- Malin Åkerblom
- , Rohit Sachdeva
- & Johan Jakobsson
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| Open AccessmiR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit
Brown fat can dissipate energy as heat and has an important role in energy homoeostasis of rodents and possibly humans. Chenet al. show that microRNA 155 regulates the differentiation of brown adipocytes as well as the 'browning' of white fat cells in mice.
- Yong Chen
- , Franziska Siegel
- & Alexander Pfeifer
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MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11
The role of microRNAs in chemotherapy resistance remains to be elucidated. Bockhorn et al.report that microRNA-30c, a human breast tumour prognostic marker, has a key role by targeting the epithelial-to-mesenchymal transition promoter twinfilin 1 and downstream interleukin-11 expression.
- Jessica Bockhorn
- , Rachel Dalton
- & Huiping Liu
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Elevated oncofoetal miR-17-5p expression regulates colorectal cancer progression by repressing its target gene P130
Tumorigenesis has been likened to a form of cellular reversion to the embryonic state. Ma et al.identify a foetal miRNA as an oncogenic activator of the Wnt/β-catenin pathway in colorectal cancer, whose expression is negatively correlated with survival but is positively correlated with response to adjuvant chemotherapy.
- Yanlei Ma
- , Peng Zhang
- & Huanlong Qin
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| Open AccessEvolution of the human-specific microRNA miR-941
miRNAs simultaneously regulate a range of genes, making them potential master players in evolution. Huet al.identify a human-specific miRNA called miR-941, whose copy number remains polymorphic in modern humans, and show that miR-941 is expressed in the brain and could regulate important signalling pathways.
- Hai Yang Hu
- , Liu He
- & Philipp Khaitovich
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| Open AccessThe miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.
- Ahmet Ucar
- , Shashi K. Gupta
- & Thomas Thum
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| Open AccessEscherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans
It is known that differences in the bacterial food ofCaenorhabditis elegans can alter their behaviour. In this study, bacteria expressing two different noncoding RNAs alter the chemosensory and longevity of C. elegans, suggesting a role in modulating C. elegansphysiology.
- Huijie Liu
- , Xueren Wang
- & Ge Shan
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Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1–S phase cell cycle transition in embryonic stem cells.
- Hao-Ming Chang
- , Natalia J. Martinez
- & Richard I. Gregory
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miR-484 regulates mitochondrial network through targeting Fis1
Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.
- Kun Wang
- , Bo Long
- & Pei-Feng Li
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miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia
HOX9AandMEIS1are key oncogenes in MLL-rearranged leukaemia. miRNA-196b is shown here to directly suppress their expression and delay MLL-fusion-mediated leukaemia, but to also cause an aggressive leukaemia phenotype when expressed ectopically, suggesting that it targets tumour suppressors as well.
- Zejuan Li
- , Hao Huang
- & Jianjun Chen
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| Open AccessGenome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
microRNAs are known to be deregulated in cancer. Using a screen for microRNAs that alter cell migration, Zhanget al. show that mir-23b blocks cell migration in vitro and in vivoand is reduced in expression in human colon cancer, suggesting a therapeutic potential for this microRNA.
- Hanshuo Zhang
- , Yang Hao
- & Jianzhong Jeff Xi
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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| Open AccessSelective inhibition of microRNA accessibility by RBM38 is required for p53 activity
MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.
- Nicolas Léveillé
- , Ran Elkon
- & Reuven Agami
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MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma
α-fetoprotein is used as a biomarker of hepatocellular cancer but the mechanisms that lead to its elevated expression are unknown. Kojimaet al.show that microRNA122 and CUX1 are important for the regulation of α-fetoprotein and suggest that loss of microRNA122 leads to more aggressive liver cancer.
- Kentaro Kojima
- , Akemi Takata
- & Kazuhiko Koike