Abstract:
:Plant microRNAs (miRNAs) are critical regulators of gene expression, however little attention has been given to the principles governing miRNA silencing efficacy. Here, we utilize the highly conserved Arabidopsis miR159-MYB33/MYB65 regulatory module to explore these principles. Firstly, we show that perfect central complementarity is not required for strong silencing. Artificial miR159 variants with two cleavage site mismatches can potently silence MYB33/MYB65, fully complementing a loss-of-function mir159 mutant. Moreover, these miR159 variants can cleave MYB33/MYB65 mRNA, however cleavage appears attenuated, as the ratio of cleavage products to full length transcripts decreases with increasing central mismatches. Nevertheless, high levels of un-cleaved MYB33/MYB65 transcripts are strongly silenced by a non-cleavage mechanism. Contrary to MIR159a variants that strongly silenced endogenous MYB33/MYB65, artificial MYB33 variants with central mismatches to miR159 are not efficiently silenced. We demonstrate that differences in the miRNA:target mRNA stoichiometry underlie this paradox. Increasing miR159 abundance in the MYB33 variants results in a strong silencing outcome, whereas increasing MYB33 transcript levels in the MIR159a variants results in a poor silencing outcome. Finally, we identify highly conserved nucleotides that flank the miR159 binding site in MYB33, and demonstrate that they are critical for efficient silencing, as mutation of these flanking nucleotides attenuates silencing at a level similar to that of central mismatches. This implies that the context in which the miRNA binding site resides is a key determinant in controlling the degree of silencing and that a miRNA "target site" encompasses sequences that extend beyond the miRNA binding site. In conclusion, our findings dismiss the notion that miRNA:target complementarity, underpinned by central matches, is the sole dictator of the silencing outcome.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Li J,Reichel M,Millar AAdoi
10.1371/journal.pgen.1004232subject
Has Abstractpub_date
2014-03-13 00:00:00pages
e1004232issue
3eissn
1553-7390issn
1553-7404pii
PGENETICS-D-13-01159journal_volume
10pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005954
更新日期:2016-04-15 00:00:00
abstract::Pregnancy-induced noncoding RNA (PINC) and retinoblastoma-associated protein 46 (RbAp46) are upregulated in alveolar cells of the mammary gland during pregnancy and persist in alveolar cells that remain in the regressed lobules following involution. The cells that survive involution are thought to function as alveolar...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002840
更新日期:2012-01-01 00:00:00
abstract::The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006414
更新日期:2016-11-07 00:00:00
abstract::DNA methylation is an ancient molecular modification found in most eukaryotes. In plants, DNA methylation is not only critical for transcriptionally silencing transposons, but can also affect phenotype by altering expression of protein coding genes. The extent of its contribution to phenotypic diversity over evolution...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004785
更新日期:2014-11-13 00:00:00
abstract::Genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants associated with various phenotypes, but together they explain only a fraction of heritability, suggesting many variants have yet to be discovered. Recently it has been recognized that incorporating functional info...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008947
更新日期:2020-08-24 00:00:00
abstract::Cereal endosperm represents 60% of the calories consumed by human beings worldwide. In addition, cereals also serve as the primary feedstock for livestock. However, the regulatory mechanism of cereal endosperm and seed development is largely unknown. Polycomb complex has been shown to play a key role in the regulation...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003322
更新日期:2013-01-01 00:00:00
abstract::Using data from primates, we show that molecular clocks in sites that have been part of a CpG dinucleotide in recent past (CpG sites) and non-CpG sites are of markedly different nature, reflecting differences in their molecular origins. Notably, single nucleotide substitutions at non-CpG sites show clear generation-ti...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020163
更新日期:2006-10-06 00:00:00
abstract::Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers o...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007380
更新日期:2018-05-07 00:00:00
abstract::We recently reported that centrosomal protein 164 (CEP164) regulates both cilia and the DNA damage response in the autosomal recessive polycystic kidney disease nephronophthisis. Here we examine the functional role of CEP164 in nephronophthisis-related ciliopathies and concomitant fibrosis. Live cell imaging of RPE-FU...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004594
更新日期:2014-10-23 00:00:00
abstract::Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme whose function is important for the biosynthesis of purines, pyrimidines, and pyridines. Importantly, while missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome, how they contribute to neuropathogenesis...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008376
更新日期:2019-09-05 00:00:00
abstract::Mating-type switching is a complex mechanism that promotes sexual reproduction in Saccharomycotina. In the model species Saccharomyces cerevisiae, mating-type switching is initiated by the Ho endonuclease that performs a site-specific double-strand break (DSB) at MAT, repaired by homologous recombination (HR) using on...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008627
更新日期:2020-10-15 00:00:00
abstract::Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by va...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000004
更新日期:2008-02-29 00:00:00
abstract::Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth and human imprinting disorder resulting from the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5. Most cases are sporadic and result from epimutations at either of the two 11p15.5 imprinting centre...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000423
更新日期:2009-03-01 00:00:00
abstract::Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in female fertility. In the Lacaune sheep breed, large variation in litter size is genetically determined by the segregation of a fecundity major gene influencing ovulation rate, named FecL and its prolific allele FecL(L) . Ou...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003809
更新日期:2013-01-01 00:00:00
abstract::The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we teste...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003220
更新日期:2013-01-01 00:00:00
abstract::Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004264
更新日期:2014-04-03 00:00:00
abstract::Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene express...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002789
更新日期:2012-06-01 00:00:00
abstract::Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005907
更新日期:2016-03-15 00:00:00
abstract::Conjugative transfer of the integrative and conjugative element ICEclc in the bacterium Pseudomonas knackmussii is the consequence of a bistable decision taken in some 3% of cells in a population during stationary phase. Here we study the possible control exerted by the stationary phase sigma factor RpoS on the bistab...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002818
更新日期:2012-01-01 00:00:00
abstract::Orienting the causal relationship between pairs of traits is a fundamental task in scientific research with significant implications in practice, such as in prioritizing molecular targets and modifiable risk factors for developing therapeutic and interventional strategies for complex diseases. A recent method, called ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009105
更新日期:2020-11-02 00:00:00
abstract::Massively parallel pyrosequencing of hypervariable regions from small subunit ribosomal RNA (SSU rRNA) genes can sample a microbial community two or three orders of magnitude more deeply per dollar and per hour than capillary sequencing of full-length SSU rRNA. As with full-length rRNA surveys, each sequence read is a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000255
更新日期:2008-11-01 00:00:00
abstract::Release factors (RFs) govern the termination phase of protein synthesis. Human mitochondria harbor four different members of the class 1 RF family: RF1Lmt/mtRF1a, RF1mt, C12orf65 and ICT1. The homolog of the essential ICT1 factor is widely distributed in bacteria and organelles and has the peculiar feature in human mi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004616
更新日期:2014-09-18 00:00:00
abstract::Escherichia coli translation initiation factor 2 (IF2) performs the unexpected function of promoting transition from recombination to replication during bacteriophage Mu transposition in vitro, leading to initiation by replication restart proteins. This function has suggested a role of IF2 in engaging cellular restart...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002648
更新日期:2012-01-01 00:00:00
abstract::Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001256
更新日期:2010-12-23 00:00:00
abstract::Recent genome-wide meta-analyses identified 157 loci associated with cross-sectional lipid traits. Here we tested whether these loci associate (singly and in trait-specific genetic risk scores [GRS]) with longitudinal changes in total cholesterol (TC) and triglyceride (TG) levels in a population-based prospective coho...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004388
更新日期:2014-06-12 00:00:00
abstract::Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleo...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002290
更新日期:2011-09-01 00:00:00
abstract::Genomic instability is a hallmark of human cancer cells. To prevent genomic instability, chromosomal DNA is faithfully duplicated in every cell division cycle, and eukaryotic cells have complex regulatory mechanisms to achieve this goal. Here, we show that untimely activation of replication origins during the G1 phase...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002136
更新日期:2011-06-01 00:00:00
abstract::Rare individuals with inactivating mutations in the Huntington's disease gene (HTT) exhibit variable abnormalities that imply essential HTT roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt, (HdhneoQ20, HdhneoQ50, HdhneoQ1...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007765
更新日期:2019-03-21 00:00:00
abstract::Seam cells in Caenorhabditis elegans provide a paradigm for the stem cell mode of division, with the ability to both self-renew and produce daughters that differentiate. The transcription factor RNT-1 and its DNA binding partner BRO-1 (homologues of the mammalian cancer-associated stem cell regulators RUNX and CBFβ, r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002200
更新日期:2011-08-01 00:00:00
abstract::In many cases protein assemblies are stabilized by covalent bonds, one example of which is the formation of intra- or intermolecular ε-(γ-glutamyl)lysil cross-links catalyzed by transglutaminases (TGases). Because of the potential for unwanted cross-linking reactions, the activities of many TGases have been shown to b...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007912
更新日期:2019-04-08 00:00:00