miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.


:miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowing transition from an immature state characterized by expression of smooth muscle (SM) genes to a more mature fetal phenotype. Concomitant knockout of miR-1-1/133a-2 and miR-1-2/133a-1 released suppression of the transcriptional co-activator myocardin, a major regulator of SM gene expression, but not of its binding partner SRF. Overexpression of myocardin in the embryonic heart essentially recapitulated the miR-1/133a mutant phenotype at the molecular level, arresting embryonic cardiomyocytes in an immature state. Interestingly, the majority of postulated miR-1/133a targets was not altered in double mutant mice, indicating that the ability of miR-1/133a to suppress target molecules strongly depends on the cellular context. Finally, we show that myocardin positively regulates expression of miR-1/133a, thus constituting a negative feedback loop that is essential for early cardiac development.


PLoS Genet


PLoS genetics


Wystub K,Besser J,Bachmann A,Boettger T,Braun T




Has Abstract


2013-01-01 00:00:00














  • Patterns of positive selection in six Mammalian genomes.

    abstract::Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small numbers of available gen...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Kosiol C,Vinar T,da Fonseca RR,Hubisz MJ,Bustamante CD,Nielsen R,Siepel A

    更新日期:2008-08-01 00:00:00

  • The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.

    abstract::Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 an...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Imai Y,Kobayashi Y,Inoshita T,Meng H,Arano T,Uemura K,Asano T,Yoshimi K,Zhang CL,Matsumoto G,Ohtsuka T,Kageyama R,Kiyonari H,Shioi G,Nukina N,Hattori N,Takahashi R

    更新日期:2015-09-10 00:00:00

  • Mis-spliced transcripts of nicotinic acetylcholine receptor alpha6 are associated with field evolved spinosad resistance in Plutella xylostella (L.).

    abstract::The evolution of insecticide resistance is a global constraint to agricultural production. Spinosad is a new, low-environmental-risk insecticide that primarily targets nicotinic acetylcholine receptors (nAChR) and is effective against a wide range of pest species. However, after only a few years of application, field ...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Baxter SW,Chen M,Dawson A,Zhao JZ,Vogel H,Shelton AM,Heckel DG,Jiggins CD

    更新日期:2010-01-01 00:00:00

  • Early back-to-Africa migration into the Horn of Africa.

    abstract::Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive o...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Hodgson JA,Mulligan CJ,Al-Meeri A,Raaum RL

    更新日期:2014-06-12 00:00:00

  • Pre-mRNA secondary structures influence exon recognition.

    abstract::The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentall...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Hiller M,Zhang Z,Backofen R,Stamm S

    更新日期:2007-11-01 00:00:00

  • Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.

    abstract::Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Sakurai D,Zhao J,Deng Y,Kelly JA,Brown EE,Harley JB,Bae SC,Alarcόn-Riquelme ME,BIOLUPUS and GENLES networks.,Edberg JC,Kimberly RP,Ramsey-Goldman R,Petri MA,Reveille JD,Vilá LM,Alarcón GS,Kaufman KM,Vyse TJ,Jacob CO,

    更新日期:2013-01-01 00:00:00

  • Genetic basis of metabolome variation in yeast.

    abstract::Metabolism, the conversion of nutrients into usable energy and biochemical building blocks, is an essential feature of all cells. The genetic factors responsible for inter-individual metabolic variability remain poorly understood. To investigate genetic causes of metabolome variation, we measured the concentrations of...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Breunig JS,Hackett SR,Rabinowitz JD,Kruglyak L

    更新日期:2014-03-06 00:00:00

  • Suppressor mutations reveal an NtrC-like response regulator, NmpR, for modulation of Type-IV Pili-dependent motility in Myxococcus xanthus.

    abstract::Two-component signaling systems (TCS) regulate bacterial responses to environmental signals through the process of protein phosphorylation. Specifically, sensor histidine kinases (SK) recognize signals and propagate the response via phosphorylation of a cognate response regulator (RR) that functions to initiate transc...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Bretl DJ,Ladd KM,Atkinson SN,Müller S,Kirby JR

    更新日期:2018-10-22 00:00:00

  • The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction.

    abstract::The C. elegans ortholog of mammalian calsyntenins, CASY-1, is an evolutionarily conserved type-I transmembrane protein that is highly enriched in the nervous system. Mammalian calsyntenins are strongly expressed at inhibitory synapses, but their role in synapse development and function is still elusive. Here, we repor...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Thapliyal S,Vasudevan A,Dong Y,Bai J,Koushika SP,Babu K

    更新日期:2018-03-12 00:00:00

  • Topoisomerase II is required for the proper separation of heterochromatic regions during Drosophila melanogaster female meiosis.

    abstract::Heterochromatic homology ensures the segregation of achiasmate chromosomes during meiosis I in Drosophila melanogaster females, perhaps as a consequence of the heterochromatic threads that connect achiasmate homologs during prometaphase I. Here, we ask how these threads, and other possible heterochromatic entanglement...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Hughes SE,Hawley RS

    更新日期:2014-10-23 00:00:00

  • Lethality of mice bearing a knockout of the Ngly1-gene is partially rescued by the additional deletion of the Engase gene.

    abstract::The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating enzyme that is highly conserved among eukaryotes. It was recently reported that subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms (NGLY1-deficiency). While the enzyme obviously has a critical role in mammals,...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Fujihira H,Masahara-Negishi Y,Tamura M,Huang C,Harada Y,Wakana S,Takakura D,Kawasaki N,Taniguchi N,Kondoh G,Yamashita T,Funakoshi Y,Suzuki T

    更新日期:2017-04-20 00:00:00

  • Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt".

    abstract::Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects population...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Gouveia MH,Bergen AW,Borda V,Nunes K,Leal TP,Ogwang MD,Yeboah ED,Mensah JE,Kinyera T,Otim I,Nabalende H,Legason ID,Mpoloka SW,Mokone GG,Kerchan P,Bhatia K,Reynolds SJ,Birtwum RB,Adjei AA,Tettey Y,Tay E,Hoover R

    更新日期:2019-03-08 00:00:00

  • AVPR1a and SLC6A4 gene polymorphisms are associated with creative dance performance.

    abstract::Dancing, which is integrally related to music, likely has its origins close to the birth of Homo sapiens, and throughout our history, dancing has been universally practiced in all societies. We hypothesized that there are differences among individuals in aptitude, propensity, and need for dancing that may partially be...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Bachner-Melman R,Dina C,Zohar AH,Constantini N,Lerer E,Hoch S,Sella S,Nemanov L,Gritsenko I,Lichtenberg P,Granot R,Ebstein RP

    更新日期:2005-09-01 00:00:00

  • Bayesian multivariate reanalysis of large genetic studies identifies many new associations.

    abstract::Genome-wide association studies (GWAS) have now been conducted for hundreds of phenotypes of relevance to human health. Many such GWAS involve multiple closely-related phenotypes collected on the same samples. However, the vast majority of these GWAS have been analyzed using simple univariate analyses, which consider ...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Turchin MC,Stephens M

    更新日期:2019-10-09 00:00:00

  • RAD50 is required for efficient initiation of resection and recombinational repair at random, gamma-induced double-strand break ends.

    abstract::Resection of DNA double-strand break (DSB) ends is generally considered a critical determinant in pathways of DSB repair and genome stability. Unlike for enzymatically induced site-specific DSBs, little is known about processing of random "dirty-ended" DSBs created by DNA damaging agents such as ionizing radiation. He...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Westmoreland J,Ma W,Yan Y,Van Hulle K,Malkova A,Resnick MA

    更新日期:2009-09-01 00:00:00

  • Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

    abstract::Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Mansour TA,Lucot K,Konopelski SE,Dickinson PJ,Sturges BK,Vernau KL,Choi S,Stern JA,Thomasy SM,Döring S,Verstraete FJM,Johnson EG,York D,Rebhun RB,Ho HH,Brown CT,Bannasch DL

    更新日期:2018-12-06 00:00:00

  • A single enhancer regulating the differential expression of duplicated red-sensitive opsin genes in zebrafish.

    abstract::A fundamental step in the evolution of the visual system is the gene duplication of visual opsins and differentiation between the duplicates in absorption spectra and expression pattern in the retina. However, our understanding of the mechanism of expression differentiation is far behind that of spectral tuning of ops...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Tsujimura T,Hosoya T,Kawamura S

    更新日期:2010-12-16 00:00:00

  • A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse.

    abstract::Intragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Conflicts over sex chromosome transmission are expected to have influenced genome structure, gene regulation, and speciation. In the mouse, the existence of an intragenomic conflict between X- and Y-linked mult...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Cocquet J,Ellis PJ,Mahadevaiah SK,Affara NA,Vaiman D,Burgoyne PS

    更新日期:2012-09-01 00:00:00

  • Speciation and introgression between Mimulus nasutus and Mimulus guttatus.

    abstract::Mimulus guttatus and M. nasutus are an evolutionary and ecological model sister species pair differentiated by ecology, mating system, and partial reproductive isolation. Despite extensive research on this system, the history of divergence and differentiation in this sister pair is unclear. We present and analyze a po...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Brandvain Y,Kenney AM,Flagel L,Coop G,Sweigart AL

    更新日期:2014-06-26 00:00:00

  • Differential effects of RASA3 mutations on hematopoiesis are profoundly influenced by genetic background and molecular variant.

    abstract::Studies of the severely pancytopenic scat mouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survival in utero; germline deletion is lethal at E12.5-13.5 due to severe hemorrhage. Here, conditional deletion in hematopoie...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Robledo RF,Ciciotte SL,Graber JH,Zhao Y,Lambert AJ,Gwynn B,Maki NJ,Brindley EC,Hartman E,Blanc L,Peters LL

    更新日期:2020-12-28 00:00:00

  • Mouse BAZ1A (ACF1) is dispensable for double-strand break repair but is essential for averting improper gene expression during spermatogenesis.

    abstract::ATP-dependent chromatin remodelers control DNA access for transcription, recombination, and other processes. Acf1 (also known as BAZ1A in mammals) is a defining subunit of the conserved ISWI-family chromatin remodelers ACF and CHRAC, first purified over 15 years ago from Drosophila melanogaster embryos. Much is known ...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Dowdle JA,Mehta M,Kass EM,Vuong BQ,Inagaki A,Egli D,Jasin M,Keeney S

    更新日期:2013-11-01 00:00:00

  • Recruitment of the Ulp2 protease to the inner kinetochore prevents its hyper-sumoylation to ensure accurate chromosome segregation.

    abstract::The kinetochore is the central molecular machine that drives chromosome segregation in all eukaryotes. Genetic studies have suggested that protein sumoylation plays a role in regulating the inner kinetochore; however, the mechanism remains elusive. Here, we show that Saccharomyces cerevisiae Ulp2, an evolutionarily co...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Suhandynata RT,Quan Y,Yang Y,Yuan WT,Albuquerque CP,Zhou H

    更新日期:2019-11-20 00:00:00

  • Deep genome-wide measurement of meiotic gene conversion using tetrad analysis in Arabidopsis thaliana.

    abstract::Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion i...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Sun Y,Ambrose JH,Haughey BS,Webster TD,Pierrie SN,Muñoz DF,Wellman EC,Cherian S,Lewis SM,Berchowitz LE,Copenhaver GP

    更新日期:2012-01-01 00:00:00

  • Genetic diversity in the interference selection limit.

    abstract::Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasi...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Good BH,Walczak AM,Neher RA,Desai MM

    更新日期:2014-03-27 00:00:00

  • Secrets of soil survival revealed by the genome sequence of Arthrobacter aurescens TC1.

    abstract::Arthrobacter sp. strains are among the most frequently isolated, indigenous, aerobic bacterial genera found in soils. Member of the genus are metabolically and ecologically diverse and have the ability to survive in environmentally harsh conditions for extended periods of time. The genome of Arthrobacter aurescens str...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Mongodin EF,Shapir N,Daugherty SC,DeBoy RT,Emerson JB,Shvartzbeyn A,Radune D,Vamathevan J,Riggs F,Grinberg V,Khouri H,Wackett LP,Nelson KE,Sadowsky MJ

    更新日期:2006-12-01 00:00:00

  • Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    abstract::High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circula...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Bigham A,Bauchet M,Pinto D,Mao X,Akey JM,Mei R,Scherer SW,Julian CG,Wilson MJ,López Herráez D,Brutsaert T,Parra EJ,Moore LG,Shriver MD

    更新日期:2010-09-09 00:00:00

  • Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extension.

    abstract::High glucose diets are unhealthy, although the mechanisms by which elevated glucose is harmful to whole animal physiology are not well understood. In Caenorhabditis elegans, high glucose shortens lifespan, while chemically inflicted glucose restriction promotes longevity. We investigated the impact of glucose metaboli...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Onken B,Kalinava N,Driscoll M

    更新日期:2020-08-25 00:00:00

  • Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity.

    abstract::Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer's disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into ...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Ando K,Maruko-Otake A,Ohtake Y,Hayashishita M,Sekiya M,Iijima KM

    更新日期:2016-03-29 00:00:00

  • A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.

    abstract::Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Skotnicka D,Smaldone GT,Petters T,Trampari E,Liang J,Kaever V,Malone JG,Singer M,Søgaard-Andersen L

    更新日期:2016-05-23 00:00:00

  • Targeting the X chromosome during spermatogenesis induces Y chromosome transmission ratio distortion and early dominant embryo lethality in Anopheles gambiae.

    abstract::We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-car...

    journal_title:PLoS genetics

    pub_type: 杂志文章


    authors: Windbichler N,Papathanos PA,Crisanti A

    更新日期:2008-12-01 00:00:00