Abstract:
:Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high messenger RNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a range of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25-nucleotide 'TINCR box' motif that is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyse TINCR binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of TINCR RNA to the staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay, however, did not have differentiation effects. Instead, the TINCR-STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through lncRNA binding to differentiation mRNAs to ensure their expression.
journal_name
Naturejournal_title
Natureauthors
Kretz M,Siprashvili Z,Chu C,Webster DE,Zehnder A,Qu K,Lee CS,Flockhart RJ,Groff AF,Chow J,Johnston D,Kim GE,Spitale RC,Flynn RA,Zheng GX,Aiyer S,Raj A,Rinn JL,Chang HY,Khavari PAdoi
10.1038/nature11661subject
Has Abstractpub_date
2013-01-10 00:00:00pages
231-5issue
7431eissn
0028-0836issn
1476-4687pii
nature11661journal_volume
493pub_type
杂志文章相关文献
NATURE文献大全abstract::Autism spectrum disorder (ASD) is an early-onset developmental disorder characterized by deficits in communication and social interaction and restrictive or repetitive behaviours1,2. Family studies demonstrate that ASD has a substantial genetic basis with contributions both from inherited and de novo variants3,4. It h...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-03078-7
更新日期:2021-01-01 00:00:00
abstract::The ability to generate patient-specific human induced pluripotent stem cells (iPSCs) offers a new paradigm for modelling human disease and for individualizing drug testing. Congenital long QT syndrome (LQTS) is a familial arrhythmogenic syndrome characterized by abnormal ion channel function and sudden cardiac death....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09747
更新日期:2011-03-10 00:00:00
abstract::Endophilin I is a presynaptic protein of unknown function that binds to dynamin, a GTPase that is implicated in endocytosis and recycling of synaptic vesicles. Here we show that endophilin I is essential for the formation of synaptic-like microvesicles (SLMVs) from the plasma membrane. Endophilin I exhibits lysophosph...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/43613
更新日期:1999-09-09 00:00:00
abstract::Understanding the capacity of natural populations to adapt to their local environment is a central topic in evolutionary biology. Phenotypic differences between populations may have a genetic basis, but showing that they reflect different adaptive optima requires the quantification of both gene flow and selection. Goo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03083
更新日期:2005-01-06 00:00:00
abstract::Villin is an actin-binding protein of relative molecular mass (Mr) 95,000 found in the core bundle of microfilaments in brush border microvilli from intestine. In physiological calcium concentrations (less than 1 microM), villin crosslinks actin filaments into bundles. However, in free calcium concentrations (greater ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/315248a0
更新日期:1985-05-16 00:00:00
abstract::Most neurons of the mammalian central nervous system (CNS) lose the ability to regenerate severed axons in vivo after a certain point in development. At least part of this loss in regenerative potential is intrinsic to neurons. Although embryonic retinal ganglion cells (RGCs) can grow axons into tectum of any age, mos...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/385434a0
更新日期:1997-01-30 00:00:00
abstract::RNA polymerase II (RNAP II) is responsible for transcribing all messenger RNAs in eukaryotic cells during a highly regulated process that is conserved from yeast to human, and that serves as a central control point for cellular function. Here we investigate the transcription dynamics of single RNAP II molecules from S...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05701
更新日期:2007-04-12 00:00:00
abstract::Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium. Sequestration may protect the parasite ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/318064a0
更新日期:1985-11-07 00:00:00
abstract::The majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, HIV, Ebola and SARS). Understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals f...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature22975
更新日期:2017-06-29 00:00:00
abstract::The crab Xenograpsus testudinatus lives at enormously high densities around the sulphur-rich hydrothermal vents found in shallow waters off Taiwan, even though this acidic environment is low in nutrients. Here we show that these crabs swarm out of their crevices at slack water and feed on the vast numbers of zooplankt...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/432969a
更新日期:2004-12-23 00:00:00
abstract::Males and females share many traits that have a common genetic basis; however, selection on these traits often differs between the sexes, leading to sexual conflict. Under such sexual antagonism, theory predicts the evolution of genetic architectures that resolve this sexual conflict. Yet, despite intense theoretical ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16062
更新日期:2015-12-17 00:00:00
abstract::Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor ho...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04892
更新日期:2006-08-31 00:00:00
abstract::The ability to form integrated circuits on flexible sheets of plastic enables attributes (for example conformal and flexible formats and lightweight and shock resistant construction) in electronic devices that are difficult or impossible to achieve with technologies that use semiconductor wafers or glass plates as sub...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07110
更新日期:2008-07-24 00:00:00
abstract::The subsidence history of the Bahamian Platform points to a non-uniform rate of sea-floor spreading since the beginning of the Cretaceous. Lower Cretaceous rates of perhaps 5 cm/yr led to an active trench system at the boundary between the American and Caribbean lithosphere plates, and the rapid subsidence of the cont...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/2251226a0
更新日期:1970-03-28 00:00:00
abstract::Interest in attributing the risk of damaging weather-related events to anthropogenic climate change is increasing. Yet climate models used to study the attribution problem typically do not resolve the weather systems associated with damaging events such as the UK floods of October and November 2000. Occurring during t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09762
更新日期:2011-02-17 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07109-2
更新日期:2018-10-01 00:00:00
abstract::In the Methods section of this Article, 'greater than' should have been 'less than' in the sentence 'Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distance that was at least 10 times greater than the whole-genome average for the individual sample. '. The Article ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41586-019-0883-2
更新日期:2019-02-01 00:00:00
abstract::Three Hipparion trails, two from adults and one from a juvenile dating from about 3.5 Myr ago, have now been found in Laetoli. Comparison of the Hipparion footprints with a variety of imprints made by domestic horses showed that the animals moved with a running walk over the soft and slippery soil of Laetoli: in the a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/308179a0
更新日期:1984-03-08 00:00:00
abstract::Derivatives of the yeast GCN4 transcription factor containing acidic regions of 35 to 40 amino acids fused directly to the DNA-binding domain are fully functional in vivo. High resolution deletion analysis and proteolytic mapping suggest that the activation region is a repeated structure composed of small units acting...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/333635a0
更新日期:1988-06-16 00:00:00
abstract::The internal organization of eukaryotic cells into functionally specialized, membrane-delimited organelles of unique composition implies a need for active, regulated lipid transport. Phosphatidylserine (PS), for example, is synthesized in the endoplasmic reticulum and then preferentially associates--through mechanisms...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12430
更新日期:2013-09-12 00:00:00
abstract::Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we rep...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature19323
更新日期:2016-09-01 00:00:00
abstract::A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three am...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2228-6
更新日期:2020-06-01 00:00:00
abstract::Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in c...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10812
更新日期:2012-02-19 00:00:00
abstract::Networks of interacting proteins orchestrate the responses of living cells to a variety of external stimuli, but how sensitive is the functioning of these protein networks to variations in their biochemical parameters? One possibility is that to achieve appropriate function, the reaction rate constants and enzyme conc...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/16483
更新日期:1999-01-14 00:00:00
abstract::Concern about the levels of lead in blood is widespread. There is uncertainty, however, about the relative importance of the various environmental sources. Lead in petrol is widely assumed to be one of the most important sources and air and dust have been identified as the main routes to man. Water is regarded as an i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/310138a0
更新日期:1984-07-12 00:00:00
abstract::Tumour suppressor genes (TSGs) inhibiting normal cellular growth are frequently silenced epigenetically in cancer. DNA methylation is commonly associated with TSG silencing, yet mutations in the DNA methylation initiation and recognition machinery in carcinogenesis are unknown. An intriguing possible mechanism for gen...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06468
更新日期:2008-01-10 00:00:00
abstract::A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer c...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06487
更新日期:2008-01-10 00:00:00
abstract::Major histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the alpha beta T-cell antigen receptor (TCR). An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CD1 molecules, a family of non-polymorphic, beta ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/372691a0
更新日期:1994-12-15 00:00:00
abstract::The difficulty of working with the intact brain in vivo has led to the increasing use of nerve cell cultures in neurobiology. However, dissociated cells cannot be unambiguously identified by morphological criteria before the third week in culture, for it is not until then that the basic morphology and size of neurones...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/281376a0
更新日期:1979-10-04 00:00:00
abstract::Anti-cancer agents that have been made selective for tumour cells by exploiting the known differences in the availability of oxygen between normal and transformed cells are a promising development in cancer chemotherapy. We have recently suggested a new type of bioreductive activity which would depend on a two-electro...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/334080a0
更新日期:1988-07-07 00:00:00