Abstract:
:How RNA-binding proteins recognize specific sets of target mRNAs remains poorly understood because current approaches depend primarily on sequence information. In this study, we demonstrate that specific recognition of messenger RNAs (mRNAs) by RNA-binding proteins requires the correct spatial positioning of these sequences. We characterized both the cis-acting sequence elements and the spatial restraints that define the mode of RNA binding of the zipcode-binding protein 1 (ZBP1/IMP1/IGF2BP1) to the β-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element comprised of a 5' element (CGGAC) followed by a variable 3' element (C/A-CA-C/U) that must be appropriately spaced. Remarkably, the orientation of these elements is interchangeable within target transcripts bound by ZBP1. The spatial relationship of this consensus binding site identified conserved transcripts that were verified to associate with ZBP1 in vivo. The dendritic localization of one of these transcripts, spinophilin, was found to be dependent on both ZBP1 and the RNA elements recognized by ZBP1 KH34.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Patel VL,Mitra S,Harris R,Buxbaum AR,Lionnet T,Brenowitz M,Girvin M,Levy M,Almo SC,Singer RH,Chao JAdoi
10.1101/gad.177428.111subject
Has Abstractpub_date
2012-01-01 00:00:00pages
43-53issue
1eissn
0890-9369issn
1549-5477pii
26/1/43journal_volume
26pub_type
杂志文章abstract::We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knocko...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.22.2894
更新日期:1996-11-15 00:00:00
abstract::3' end formation of pre-mRNAs is coupled to their transcription via the C-terminal domain (CTD) of RNA polymerase II (Pol II). Nearly all protein-coding transcripts are matured by cleavage and polyadenylation (CPA), which is frequently misregulated in disease. Understanding how transcription is coordinated with CPA in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.231274.113
更新日期:2014-02-15 00:00:00
abstract::Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of ci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1194004
更新日期:2004-07-01 00:00:00
abstract::Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1825809
更新日期:2009-09-15 00:00:00
abstract::The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.243584.114
更新日期:2014-10-15 00:00:00
abstract::The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼ 500-residue N-terminal region, whose functions and mo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271528.115
更新日期:2015-12-15 00:00:00
abstract::Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1270
更新日期:1994-06-01 00:00:00
abstract::Cell cycle transitions are often accompanied by the degradation of regulatory molecules. Targeting proteins to the proteasome for degradation is accomplished by the covalent addition of ubiquitin chains. The specificity of this pathway is largely dictated by a set of enzymes called ubiquitin ligases (or E3s). The anap...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1478306
更新日期:2006-11-15 00:00:00
abstract::Transformation of primary rodent cells by the adenovirus E1A and E1B oncogenes is a two-step process, where E1A-dependent induction of proliferation is coupled to E1B-dependent suppression of programmed cell death (apoptosis). The E1B gene encodes two distinct transforming proteins, the 19K and 55K proteins, both of w...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.4.546
更新日期:1993-04-01 00:00:00
abstract::Signals from TGF-beta superfamily receptors are transduced to the nucleus by Smad proteins, which transcriptionally activate target genes. In Caenorhabditis elegans, defects in a TGF-beta-related pathway cause a reversible developmental arrest and metabolic shift at the dauer larval stage. Null mutations in daf-3 supp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.20.2679
更新日期:1997-10-15 00:00:00
abstract::In the cytoplasm of oocytes and early embryos, addition of poly(A) to mRNAs can activate their translation. We demonstrate that despite many differences between poly(A) addition in the cytoplasm and nucleus, these two forms of polyadenylation may involve identical trans-acting factors. Nuclear polyadenylation requires...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.9.1106
更新日期:1994-05-01 00:00:00
abstract::Cellular signaling initiated by Hedgehog binding to Patched1 has profound importance in mammalian embryogenesis, genetic disease, and cancer. Hedgehog acts as a morphogen to specify distinctive cell fates using different concentration thresholds, but our knowledge of how the concentration gradient is interpreted into ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1546307
更新日期:2007-05-15 00:00:00
abstract::The X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals. Over recent years an important goal has been to understand how Xist is regulated at the initiation of X inactivation. Here we report the analysis of a series of targeted mutations at the 5' end o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271203
更新日期:2003-09-01 00:00:00
abstract::Interactions required for inhibition of poly(A) polymerase (PAP) by the U1 snRNP-specific U1A protein, a reaction whose function is to autoregulate U1A protein production, are examined. PAP inhibition requires a substrate RNA to which at least two molecules of U1A protein can bind tightly, but we demonstrate that the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.6.761
更新日期:1997-03-15 00:00:00
abstract::Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.1.64
更新日期:1999-01-01 00:00:00
abstract::Gene silencing by double-stranded RNA is a widespread phenomenon called RNAi, involving homology-dependent degradation of mRNAs. Here we show that RNAi is established in the Drosophila female germ line. mRNA transcripts are translationally quiescent at the arrested oocyte stage and are insensitive to RNAi. Upon oocyte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.990802
更新日期:2002-08-01 00:00:00
abstract::During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains of dorsal and ventral fate, then further patterned to generate somitic mesoderm by signals from the gastrula organizer. Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to di...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.21.2805
更新日期:1996-11-01 00:00:00
abstract::In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.179663.111
更新日期:2012-01-15 00:00:00
abstract::Faithful duplication of the genome relies on the ability to cope with an imperfect template. We investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming. Undamaged origins of replication (oriC) continue to fire at the normal rate and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417607
更新日期:2007-03-15 00:00:00
abstract::Telomere proteins protect the chromosomal terminus from nucleolytic degradation and end-to-end fusion, and they may contribute to telomere length control and the regulation of telomerase. The current studies investigate the effect of Oxytricha single-stranded telomere DNA-binding protein subunits alpha and beta on tel...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.10.1504
更新日期:1998-05-15 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a "ductal-like" state during PanIN-PDA formation. Here, we demonstrate a parallel mechanis...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256628.114
更新日期:2015-03-15 00:00:00
abstract::Our understanding of eukaryotic transcriptional activation mechanisms has been hampered by an inability to identify the direct in vivo targets of activator proteins, primarily because of lack of appropriate experimental methods. To circumvent this problem, we have developed a fluorescence resonance energy transfer (FR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1148404
更新日期:2004-02-01 00:00:00
abstract::Genetic and cytologic data from Saccharomyces cerevisiae and mammals implicate the Mre11 complex, consisting of Mre11, Rad50, and Nbs1, as a sensor of DNA damage, and indicate that the complex influences the activity of ataxia-telangiectasia mutated (ATM) in the DNA damage response. Rad50(S/S) mice exhibit precipitous...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1373705
更新日期:2005-12-15 00:00:00
abstract::Sox10 is a high-mobility-group transcriptional regulator in early neural crest. Without Sox10, no glia develop throughout the peripheral nervous system. Here we show that Sox10 is restricted in the central nervous system to myelin-forming oligodendroglia. In Sox10-deficient mice progenitors develop, but terminal diffe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.215802
更新日期:2002-01-15 00:00:00
abstract::We report a new role for Wnt signaling in the vertebrate embryo: the induction of neural tissue from ectoderm. Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm. We show that Wnt8, but...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.23.3149
更新日期:1999-12-01 00:00:00
abstract::The Drosophila somatic sex-determination regulatory pathway has been well studied, but little is known about the target genes that it ultimately controls. In a differential screen for sex-specific transcripts expressed in fly heads, we identified a highly male-enriched transcript encoding Takeout, a protein related to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1010302
更新日期:2002-11-15 00:00:00
abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.318675.118
更新日期:2018-12-01 00:00:00
abstract::Transcription of the cell-cycle-regulated human histone genes increases approximately fivefold during S phase. One step toward the elucidation of the biochemical mechanisms that govern cell-cycle-regulated expression of these genes is to purify and characterize the transcription factors that regulate these promoters. ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1700
更新日期:1988-12-01 00:00:00
abstract::Epigenetic modifications of chromatin play an important role in the regulation of gene expression. KMT4/Dot1 is a conserved histone methyltransferase capable of methylating chromatin on Lys79 of histone H3 (H3K79). Here we report the identification of a multisubunit Dot1 complex (DotCom), which includes several of the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1898410
更新日期:2010-03-15 00:00:00
abstract::In eubacteria, the ClpS adaptor has been proposed to be essential for degradation of N-end rule substrates by the AAA(+) protease ClpAP. To test this model, we assayed degradation of substrates bearing N-end rule sequences isolated in a genetic screen for efficient degradation tags. ClpS was not vital for degradation ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1511907
更新日期:2007-02-15 00:00:00