Abstract:
:Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.
journal_name
Celljournal_title
Cellauthors
Schaffer AE,Eggens VR,Caglayan AO,Reuter MS,Scott E,Coufal NG,Silhavy JL,Xue Y,Kayserili H,Yasuno K,Rosti RO,Abdellateef M,Caglar C,Kasher PR,Cazemier JL,Weterman MA,Cantagrel V,Cai N,Zweier C,Altunoglu U,Satkin Ndoi
10.1016/j.cell.2014.03.049subject
Has Abstractpub_date
2014-04-24 00:00:00pages
651-63issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(14)00478-4journal_volume
157pub_type
杂志文章相关文献
CELL文献大全abstract::Ions serve as essential nutrients in higher plants and can also act as signaling molecules. Little is known about how plants sense changes in soil nutrient concentrations. Previous studies showed that T101-phosphorylated CHL1 is a high-affinity nitrate transporter, whereas T101-dephosphorylated CHL1 is a low-affinity ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.07.004
更新日期:2009-09-18 00:00:00
abstract::Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2020.01.007
更新日期:2020-02-20 00:00:00
abstract::Among its multiple functions, p53 is a critical regulator of TGF-beta responses. Sasai et al. (2008) now identify a new p53 inhibitory protein, XFDL156. During embryonic development, this factor is expressed in the ectoderm germ layer and maintains the pluripotency of ectodermal cells by inhibiting TGF-beta target gen...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2008.05.013
更新日期:2008-05-30 00:00:00
abstract::We have determined the nucleotide sequences of the germ line gene as well as a corresponding somatically mutated and rearranged gene coding for a mouse immunoglobulin lambdaI type light chain. These sequencing studies were carried out on three Eco RI-DNA fragments which had been cloned from BALB/c mouse embryos or a l...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(78)90041-7
更新日期:1978-12-01 00:00:00
abstract::In S. cerevisiae, mitochondrial DNA (mtDNA) molecules, in spite of their high copy number, segregate as if there were a small number of heritable units. The rapid segregation of mitochondrial genomes can be analyzed using mtDNA deletion variants. These small, amplified genomes segregate preferentially from mixed zygot...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90014-4
更新日期:1995-06-16 00:00:00
abstract::The liver is capable of completely regenerating itself in response to injury and after partial hepatectomy. In liver of old animals, the proliferative response is dramatically reduced, the mechanism for which is unknown. The liver specific protein, C/EBPalpha, normally arrests proliferation of hepatocytes through inhi...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00318-0
更新日期:2003-05-16 00:00:00
abstract::We show that expression of the iso-1-cytochrome c gene of Saccharomyces cerevisiae, CYC1, is tightly regulated by levels of intracellular heme. Expression is reduced at least 200-fold in cells grown under conditions of heme deficiency. Studies on the regulation of a CYC1-lacZ fused gene and direct determination of mRN...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(83)90309-4
更新日期:1983-04-01 00:00:00
abstract::The majority of cell lines derived by infection of murine bone marrow cells with Abelson murine leukemia virus (A-MuLV) synthesize a mu chain but no detectable light chain. Aside from this mu-only phenotype, lines that make only light chain, both chains or no immunoglobulin-related polypeptides have also been found. T...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90014-x
更新日期:1979-02-01 00:00:00
abstract::Suppressor of Hairless (Su(H)) is required at two stages of adult sensory organ development in Drosophila. Complete loss of Su(H) function results in a "neurogenic" phenotype in imaginal discs, in which too many cells adopt the sensory organ precursor cell fate. Su(H) is also involved in controlling the fates of sensi...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(92)90641-o
更新日期:1992-06-26 00:00:00
abstract::Clec16a has been identified as a disease susceptibility gene for type 1 diabetes, multiple sclerosis, and adrenal dysfunction, but its function is unknown. Here we report that Clec16a is a membrane-associated endosomal protein that interacts with E3 ubiquitin ligase Nrdp1. Loss of Clec16a leads to an increase in the N...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.05.016
更新日期:2014-06-19 00:00:00
abstract::Recently, a Drosophila gene has been identified, extradenticle, whose product modulates the morphological consequences of homeotic selector genes. We show here that extradenticle protein raises the DNA binding specificity of Ultrabithorax and abdominal-A but not that of Abdominal-B. We further show that extradenticle ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90526-6
更新日期:1994-08-26 00:00:00
abstract::The human epsilon-globin gene has a number of alternative transcription-initiation sites located upstream of the canonical mRNA cap site. In three nonerythroid cell lines, "leaky" epsilon-globin transcription occurs exclusively from one of these upstream sites, the -200 cap site. Using a transient expression assay, we...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(84)90495-1
更新日期:1984-09-01 00:00:00
abstract::Telomerase activity was demonstrated in cell-free extracts from S. cerevisiae through the use of a PCR-based assay. As expected, this activity was eliminated by RNase or phenol treatment of the extract and was dependent on dGTP and dTTP. Telomerase was not detected in extracts prepared from cells grown for approximate...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(05)80017-0
更新日期:1995-06-30 00:00:00
abstract::In order to identify nucleotide sequences required for efficient and accurate polyadenylation of mRNA precursors, we have constructed a series of mutations in the X. laevis beta 1-globin gene and analyzed transcripts produced upon microinjection into Xenopus oocytes. Small deletion and linker replacement mutations, wh...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(86)90743-9
更新日期:1986-07-18 00:00:00
abstract::I have defined conditions under which RepFIC plasmid DNA can be maintained in a state of lowered helical density. In exponentially growing cultures, the DNA of lowered helical density is present in small amounts but never totally absent, suggesting that it is a normal variant of plasmid maintenance. It is fully methyl...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(01)00402-0
更新日期:2001-06-29 00:00:00
abstract::Using a defined RNA polymerase II (pol II) transcription system, we have investigated the roles of basal factors at discrete stages during the transcription cycle (e.g., initiation, promoter clearance, and transcript elongation). Abortive initiation assays revealed that TATA-binding protein, transcription factors TFII...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(94)90242-9
更新日期:1994-04-08 00:00:00
abstract::We have reproduced the posttranslational mode of protein translocation across the endoplasmic reticulum membrane with reconstituted proteoliposomes containing a purified complex of seven yeast proteins. This Sec complex includes a heterotrimeric Sec61p complex, homologous to that in mammals, as well as all other membr...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90077-2
更新日期:1995-05-19 00:00:00
abstract::The plant innate immune response includes the hypersensitive response (HR), a form of programmed cell death (PCD). PCD must be restricted to infection sites to prevent the HR from playing a pathologic rather than protective role. Here we show that plant BECLIN 1, an ortholog of the yeast and mammalian autophagy gene A...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2005.03.007
更新日期:2005-05-20 00:00:00
abstract::The Origin Recognition Complex (ORC) is a six-protein assembly that specifies the sites of DNA replication initiation in S. cerevisiae. Origin recognition by ORC requires ATP. Here, we demonstrate that two subunits, Orc1p and Orc5p, bind ATP and that Orc1p also hydrolyzes ATP. ATP binding and hydrolysis by Orc1p are b...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81889-9
更新日期:1997-02-21 00:00:00
abstract::The V(D)J recombinase subunits Rag-1 and Rag-2 mediate assembly of antigen receptor gene segments. We studied the mechanisms of DNA recognition by Rag-1/Rag-2 using surface plasmon resonance. The critical step for signal recognition is binding of Rag-1 to the nonamer. This is achieved by a region of Rag-1 homologous t...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81344-6
更新日期:1996-10-18 00:00:00
abstract::Embryonic inductions appear to be mediated by the concerted action of different inducing factors that modulate one another's activity. Such modulation is likely to reflect interactions between the signal transduction pathways through which the inducing factors act. We tested this idea for the induction of neural tissu...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(89)90099-8
更新日期:1989-08-25 00:00:00
abstract::Spinocerebellar ataxia type 1 (SCA1) is one of nine inherited, typically adult onset, polyglutamine neurodegenerative diseases. To examine whether development impacts SCA1, we used a conditional transgenic mouse model of SCA1 to delay the postnatal expression of mutant ATXN1 until after completion of cerebellar develo...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2006.09.036
更新日期:2006-11-17 00:00:00
abstract::Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating, perturbing, and engineering cellular systems. Here, we develop a method for controlling gene expression based on Cas9, an RNA-guided DNA endonuclease from a type II CRISPR system. We show that a catalytically dead Cas9 lacking en...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2013.02.022
更新日期:2013-02-28 00:00:00
abstract::RGS proteins are GTPase activators for heterotrimeric G proteins. We report here the 2.8 A resolution crystal structure of the RGS protein RGS4 complexed with G(i alpha1)-Mg2+-GDP-AlF4 . Only the core domain of RGS4 is visible in the crystal. The core domain binds to the three switch regions of G(i alpha1), but does n...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80204-4
更新日期:1997-04-18 00:00:00
abstract::Viruses are adept at evolving or co-opting genomic elements that allow them to maximize their replication potential in the infected host. This evolutionary plasticity makes viruses an invaluable system to identify new mechanisms used not only by viruses but also by vertebrate cells to modulate gene expression. Here, I...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.01.048
更新日期:2009-02-20 00:00:00
abstract::A key step in the regulation of transcription involves interactions between promoter-selective factors and various components of the transcriptional apparatus. Here we report the requirements for transcriptional activation directed by NTF-1, a developmentally regulated transcription factor in Drosophila. Reconstituted...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90019-2
更新日期:1991-08-09 00:00:00
abstract::Genetic and transcriptional maps have been constructed for the mitochondrial genome of the Ascomycete Podospora anserina. These data have been plotted on the restriction maps for Sal I, Xho I, Bam HI, Eco RI, BgI II and Hae III. We have characterized and cloned a new and unique senescent mitochondrial DNA (beta-event ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(82)90167-2
更新日期:1982-06-01 00:00:00
abstract::The replication initiator protein of the plasmid R6K binds to seven contiguous 22 bp direct repeats that form an indispensable part of the three replication origins alpha, beta, and gamma. Binding of the initiator to the direct repeats induced a marked bending of the region of gamma replication origin. Binding of the ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(85)90023-6
更新日期:1985-11-01 00:00:00
abstract::The Bcl-2 family member Bax translocates from the cytosol to mitochondria, where it oligomerizes and permeabilizes the mitochondrial outer membrane to promote apoptosis. Bax activity is counteracted by prosurvival Bcl-2 proteins, but how they inhibit Bax remains controversial because they neither colocalize nor form s...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2011.02.034
更新日期:2011-04-01 00:00:00
abstract::We employed gene targeting to study H2AX, a histone variant phosphorylated in chromatin surrounding DNA double-strand breaks. Mice deficient for both H2AX and p53 (H(delta/delta)P(-/-)) rapidly developed immature T and B lymphomas and solid tumors. Moreover, H2AX haploinsufficiency caused genomic instability in normal...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(03)00566-x
更新日期:2003-08-08 00:00:00