Featured
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Letter |
PVT1 dependence in cancer with MYC copy-number increase
Pvt1 overexpression in mice contributes to high Myc levels due to 8q24.21 gain and to MYC-driven tumorigenesis.
- Yuen-Yi Tseng
- , Branden S. Moriarity
- & Anindya Bagchi
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News & Views |
Short RNAs and shortness of breath
The simultaneous deletion of six RNA molecules in mice has been found to cause respiratory and fertility defects, owing to improper assembly of structures called cilia on the cell surface. See Article p.115
- Irma Sánchez
- & Brian D. Dynlacht
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Article |
miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110
Loss-of-function studies of the miR-34/449 microRNA family in mouse and Xenopus reveal their evolutionarily conserved role in ciliogenesis by repressing expression of the centriolar protein Cp110.
- Rui Song
- , Peter Walentek
- & Lin He
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News & Views |
Female silkworms have the sex factor
Sex determination in the silkworm Bombyx mori has been found to depend on the presence or absence of a small RNA. This is thought to be the first example of a molecule other than a protein mediating this process. See Letter p.633
- František Marec
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News |
Sperm RNA carries marks of trauma
Stress alters the expression of small RNAs in male mice and leads to depressive behaviours in later generations.
- Virginia Hughes
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Article |
An atlas of active enhancers across human cell types and tissues
Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.
- Robin Andersson
- , Claudia Gebhard
- & Albin Sandelin
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Letter |
miRNAs trigger widespread epigenetically activated siRNAs from transposons in Arabidopsis
The generation of widespread epigenetically activated short interfering RNAs by the targeting of microRNAs to transposon transcripts in Arabidopsis thaliana is shown to be a latent mechanism that only becomes active when the transcripts are epigenetically reactivated, for example, during reprogramming of the germ line.
- Kate M. Creasey
- , Jixian Zhai
- & Robert A. Martienssen
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Review Article |
PIWI proteins and PIWI-interacting RNAs in the soma
- Robert J. Ross
- , Molly M. Weiner
- & Haifan Lin
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Review Article |
The multilayered complexity of ceRNA crosstalk and competition
- Yvonne Tay
- , John Rinn
- & Pier Paolo Pandolfi
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Research Highlights |
Microbes meddle with microRNA
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Letter |
High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation
During mammalian X-chromosome inactivation, the Xist long noncoding RNA coats the future inactive X chromosome and recruits polycomb repressive complex 2 to a nucleation site, but how Xist spreads silencing across the entire X chromosome is unclear; here high-resolution maps of Xist binding sites across the X chromosome are generated and show that Xist does not spread across the inactive X chromosome uniformly but in two steps, initially targeting gene-rich islands before later spreading to intervening gene-poor domains.
- Matthew D. Simon
- , Stefan F. Pinter
- & Jeannie T. Lee
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Article |
DNMT1-interacting RNAs block gene-specific DNA methylation
RNAs are shown to interact with DNA methyltransferase 1 and prevent DNA methylation of genes at their specific locus, providing evidence that active transcription directly regulates DNA methylation levels.
- Annalisa Di Ruscio
- , Alexander K. Ebralidze
- & Daniel G. Tenen
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Research Highlights |
RNA boosts genes on a loop
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Letter |
lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs
A study of prostate cancer cells reveals a transcriptional activation role for long non-coding RNAs (PRNCR1 and PCGEM1) that bind to the androgen receptor, and is also observed for the truncated androgen receptor characteristic of many aggressive prostate cancers.
- Liuqing Yang
- , Chunru Lin
- & Michael G. Rosenfeld
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Letter |
Promoter directionality is controlled by U1 snRNP and polyadenylation signals
Asymmetric sequence determinants flanking gene transcription start sites are shown to control directionality of transcription elongation in mammalian cells by regulating promoter-proximal cleavage and polyadenylation.
- Albert E. Almada
- , Xuebing Wu
- & Phillip A. Sharp
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Letter |
Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation
It is unclear whether bidirectional non-coding RNAs transcribed from enhancer elements (eRNAs) have any functional role; here, eRNA transcription is shown to be functionally important during the activation of genes by the oestrogen receptor in human breast cancer cells.
- Wenbo Li
- , Dimple Notani
- & Michael G. Rosenfeld
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Letter |
The microRNA miR-235 couples blast-cell quiescence to the nutritional state
A microRNA, miR-235, is identified that acts downstream of the insulin/insulin growth factor signalling pathway to modulate the quiescence of blast cells in Caenorhabditis elegans.
- Hidefumi Kasuga
- , Masamitsu Fukuyama
- & Toshiaki Katada
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Letter |
Extensive transcriptional heterogeneity revealed by isoform profiling
Variation among RNA transcript isoforms can be generated from alternative start and polyadenylation sites, and results in RNAs and proteins with different properties being generated from the same genomic sequence; here a new method termed transcript isoform sequencing is described in yeast, and the method allows a fuller exploration of transcriptome diversity across the compact yeast genome.
- Vicent Pelechano
- , Wu Wei
- & Lars M. Steinmetz
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Letter |
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.
- Hao-Ming Chang
- , Robinson Triboulet
- & Richard I. Gregory
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Article |
Circular RNAs are a large class of animal RNAs with regulatory potency
Biochemical, functional and computational analyses are combined to show that circular RNAs are a large class of animal RNAs with regulatory potency.
- Sebastian Memczak
- , Marvin Jens
- & Nikolaus Rajewsky
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Letter |
Natural RNA circles function as efficient microRNA sponges
A natural circular RNA termed ciRS-7 is shown to function as a negative regulator of microRNA; ciRS-7 acts as an efficient sponge for the microRNA miR-7, and is resistant to the usual microRNA-mediated degradation pathway of exonucleolytic RNA decay.
- Thomas B. Hansen
- , Trine I. Jensen
- & Jørgen Kjems
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Letter |
MicroRNA-34a regulates cardiac ageing and function
A role is demonstrated for miR-34a, a microRNA that is upregulated in the ageing heart; miR-34a downregulates PNUTS, a protein that protects cardiomyocytes and telomeres, silencing of miR-34a is therefore a promising therapeutic target.
- Reinier A. Boon
- , Kazuma Iekushi
- & Stefanie Dimmeler
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Letter |
Activating RNAs associate with Mediator to enhance chromatin architecture and transcription
A class of long non-coding RNA (lncRNA) with enhancer-like activity is found to associate with the co-activator complex Mediator and promote its genomic association and enzymatic activity; together with Mediator, the lncRNAs also help to maintain the chromosomal architecture of active regulatory elements.
- Fan Lai
- , Ulf A. Orom
- & Ramin Shiekhattar
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Letter |
‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing
A post-transcriptional switch that controls spatiotemporal and mutually exclusive expression of two alternative gene products from a single transcript is reported; these gene products—miR-198 and FSTL1—are found to have opposing functions on keratinocyte migration and wound healing.
- Gopinath M. Sundaram
- , John E. A. Common
- & Prabha Sampath
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Letter |
Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence
To identify comprehensively factors involved in RNAi and microRNA-mediated gene expression regulation, this study performed a phylogenetic analysis of 86 eukaryotic species; the candidates this approach highlighted were subjected to Bayesian analysis with transcriptional and proteomic interaction data, identifying protein orthologues of already known RNAi silencing factors, as well as other hits involved in splicing, suggesting a connection between the two processes.
- Yuval Tabach
- , Allison C. Billi
- & Gary Ruvkun
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News & Views |
A boost for heart regeneration
Heart muscle cells die en masse after injury, yet the adult mammalian heart retains little capacity to regenerate them. Regulatory microRNA sequences may stimulate self-renewal of these muscle cells. See Article p.376
- Mark Mercola
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Article |
Functional screening identifies miRNAs inducing cardiac regeneration
The human heart regenerates poorly, causing insufficient healing after injury; here, microRNAs screened for the ability to induce cardiomyocyte proliferation are shown to stimulate cardiac regeneration and almost complete recovery of the heart after infarction.
- Ana Eulalio
- , Miguel Mano
- & Mauro Giacca
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Letter |
Control of somatic tissue differentiation by the long non-coding RNA TINCR
The human long non-coding RNA TINCR binds to STAU1 and controls epidermal differentiation by stabilizing key differentiation mRNAs, by means of a TINCR-binding motif found enriched in epidermal differentiation genes.
- Markus Kretz
- , Zurab Siprashvili
- & Paul A. Khavari
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Research Highlights |
How cold triggers fat formation
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Letter |
Structure and function of Zucchini endoribonuclease in piRNA biogenesis
Zucchini has been identified as an endoribonuclease responsible for the maturation of small RNA molecules that protect the genome from the damaging effects of unrestrained expression of mobile elements.
- Hiroshi Nishimasu
- , Hirotsugu Ishizu
- & Osamu Nureki
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Letter |
The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
piRNAs act to protect the genome from the damaging effect of unrestrained expression of mobile elements; here it is suggested that the phosphodiesterase Zucchini may be the nuclease that generates the 5′ ends of primary piRNAs.
- Jonathan J. Ipsaro
- , Astrid D. Haase
- & Gregory J. Hannon
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Letter |
Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat
Antisense Uchl1, a long non-coding RNA that is an antisense transcript for the Uchl1 gene, upregulates UCHL1 protein levels through the combined action of an overlapping sequence at its 5′ end and an embedded SINEB2 element.
- Claudia Carrieri
- , Laura Cimatti
- & Stefano Gustincich
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Letter |
Paramutation in Drosophila linked to emergence of a piRNA-producing locus
A paramutation occurs between two alleles in the same locus, when one allele induces a heritable mutation in another allele without modifying the DNA sequence; now, in Drosophila, a paramutation is shown to be transmissible over generations.
- Augustin de Vanssay
- , Anne-Laure Bougé
- & Stéphane Ronsseray
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News Feature |
Phylogeny: Rewriting evolution
Tiny molecules called microRNAs are tearing apart traditional ideas about the animal family tree.
- Elie Dolgin
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Letter |
Autoregulation of microRNA biogenesis by let-7 and Argonaute
MicroRNA in worms is shown to target non-coding primary microRNA transcripts through interaction with the Argonaute protein, promoting the production of further microRNA and thus generating a positive-feedback loop.
- Dimitrios G. Zisoulis
- , Zoya S. Kai
- & Amy E. Pasquinelli
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Research Highlights |
Small RNAs boost memory process
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Research Highlights |
MicroRNAs boost gene variation
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Research Highlights |
Noncoding RNAs decapped
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Letter |
Maintenance of muscle stem-cell quiescence by microRNA-489
Adult muscle stem cells are used as a model system to show that the microRNA pathway, and specifically miR-489, is essential for the maintenance of the quiescent state of an adult stem-cell population by suppressing a key proliferation factor, Dek.
- Tom H. Cheung
- , Navaline L. Quach
- & Thomas A. Rando
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News & Views Forum |
RNA discrimination
In the cell, genomic DNA is transcribed into various types of RNA. But not all RNAs are translated into proteins. Does this give protein-coding RNAs greater credibility in terms of function? Views differ.
- Monika S. Kowalczyk
- , Douglas R. Higgs
- & Thomas R. Gingeras
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Review Article |
Modular regulatory principles of large non-coding RNAs
- Mitchell Guttman
- & John L. Rinn
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Letter |
A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells
The microRNA miR-126 suppresses the formation of breast cancer metastases via the suppression of several novel pro-angiogenic genes that cooperate in the recruitment of endothelial cells, leading to the formation of metastatic colonies.
- Kim J. Png
- , Nils Halberg
- & Sohail F. Tavazoie
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Letter |
Image-based genome-wide siRNA screen identifies selective autophagy factors
- Anthony Orvedahl
- , Rhea Sumpter Jr.
- & Beth Levine
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Letter |
Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing
Piwi protein Miwi is shown to be a small RNA-guided RNase in mice; disrupting the catalytic activity of Miwi results in increased accumulation of LINE1 retrotransposon transcripts and male infertility.
- Michael Reuter
- , Philipp Berninger
- & Ramesh S. Pillai
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Letter |
The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements
- Serena De Fazio
- , Nenad Bartonicek
- & Dónal O’Carroll
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Article |
lincRNAs act in the circuitry controlling pluripotency and differentiation
- Mitchell Guttman
- , Julie Donaghey
- & Eric S. Lander
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Letter |
MicroRNA-mediated conversion of human fibroblasts to neurons
- Andrew S. Yoo
- , Alfred X. Sun
- & Gerald R. Crabtree
RETRACTED ARTICLE: miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2
The microcosmos of cancer