Abstract：
:tRNAs are subject to numerous modifications, including methylation. Mutations in the human N7-methylguanosine (m7G) methyltransferase complex METTL1/WDR4 cause primordial dwarfism and brain malformation, yet the molecular and cellular function in mammals is not well understood. We developed m7G methylated tRNA immunoprecipitation sequencing (MeRIP-seq) and tRNA reduction and cleavage sequencing (TRAC-seq) to reveal the m7G tRNA methylome in mouse embryonic stem cells (mESCs). A subset of 22 tRNAs is modified at a "RAGGU" motif within the variable loop. We observe increased ribosome occupancy at the corresponding codons in Mettl1 knockout mESCs, implying widespread effects on tRNA function, ribosome pausing, and mRNA translation. Translation of cell cycle genes and those associated with brain abnormalities is particularly affected. Mettl1 or Wdr4 knockout mESCs display defective self-renewal and neural differentiation. Our study uncovers the complexity of the mammalian m7G tRNA methylome and highlights its essential role in ESCs with links to human disease.
journal_name
Mol Celljournal_title
Molecular cellauthors
Lin S,Liu Q,Lelyveld VS,Choe J,Szostak JW,Gregory RIdoi
10.1016/j.molcel.2018.06.001subject
Has Abstractpub_date
2018-07-19 00:00:00pages
244-255.e5issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(18)30443-Xjournal_volume
71pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract：:Infections can cause a multitude of stresses on the host and microbe. To detect potential infections, the mammalian immune system utilizes several families of pattern recognition receptors, which survey the intracellular and extracellular environments for microbial products. Members of each receptor family induce anti...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2017.05.009
更新日期：2017-06-15 00:00:00
abstract：:Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification. We show that Ser13 of uncomplexed Cdc37 is phosphorylated in vivo, as well as in bin...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.07.021
更新日期：2008-09-26 00:00:00
abstract：:Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal m...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2018.06.034
更新日期：2018-08-02 00:00:00
abstract：:Yeast Sir2 protein regulates chromatin structure and suppresses recombination at the multiple tandem rDNA array. In the current issue of Cell, Kobayashi and colleagues reinvestigate rDNA dynamics in sir2 strains and find that Sir2 is necessary to recruit cohesins to the array, which influences the nature of rDNA recom...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/s1097-2765(04)00266-7
更新日期：2004-05-21 00:00:00
abstract：:Transcription initiation requires opening of promoter DNA in the RNA polymerase II (Pol II) pre-initiation complex (PIC), but it remains unclear how this is achieved. Here we report the cryo-electron microscopic (cryo-EM) structure of a yeast PIC that contains underwound, distorted promoter DNA in the closed Pol II cl...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.10.014
更新日期：2019-01-03 00:00:00
abstract：:Two yeast enzymes that catalyze aminoacylation of tRNAs, MetRS and GluRS, form a complex with the protein Arc1p. We show here that association of Arc1p with MetRS and GluRS is required in vivo for effective recruitment of the corresponding cognate tRNAs within this complex. Arc1p is linked to MetRS and GluRS through i...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80024-6
更新日期：1998-01-01 00:00:00
abstract：:The protective "cap" that assembles at chromosome ends recruits and controls an intricate network of biochemical activities, each one critical for telomere structure and the maintenance of genomic stability. Recent studies have uncovered the components of telomere caps and have started to define the pathways that lead...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/s1097-2765(03)00531-8
更新日期：2004-01-16 00:00:00
abstract：:X chromosome inactivation (XCI) depends on a noncoding sense-antisense transcript pair, Xist and Tsix. At the onset of XCI, Xist RNA accumulates on one of two Xs, coating and silencing the chromosome in cis. The molecular basis for monoallelic Xist upregulation is not known, though evidence predominantly supports a po...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.01.028
更新日期：2006-03-03 00:00:00
abstract：:Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced degradation. In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80133-1
更新日期：1998-08-01 00:00:00
abstract：:Although DNA looping between the initiator binding sites (iterons) of the replication origin (ori) of a plasmid and the iterons located in a cis-acting control sequence called inc has been postulated to promote negative control of plasmid DNA replication, not only was definitive evidence for such looping lacking, but ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.10.037
更新日期：2005-12-22 00:00:00
abstract：:Sister-chromatid cohesion describes the orderly association of newly replicated DNA molecules behind replication forks. It plays an essential role in the maintenance and faithful transmission of genetic information. Cohesion is created by DNA topological links and proteinaceous bridges, whose formation and deposition ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2020.06.033
更新日期：2020-09-03 00:00:00
abstract：:HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80056-8
更新日期：1998-03-01 00:00:00
abstract：:Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Several replication-fork-associated "cohesion establishment factors," including the multifunctional Ctf18-RFC complex, aid this process in as yet unknown ways. Here, we show that Ctf18-RFC...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2020.03.017
更新日期：2020-05-21 00:00:00
abstract：:Activation of NF-kappaB is regulated via numerous ubiquitin- and proteasome-mediated steps; an important one is processing of the precursor p105 to the p50 active subunit. The mechanisms involved are largely unknown, because this is an exceptional case where the ubiquitin system does not destroy its substrate complete...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2009.01.023
更新日期：2009-02-27 00:00:00
abstract：:Replication forks frequently break and must be repaired by recombination. A reconstituted reaction now allows the factors that coordinate conversion from a recombination intermediate back to a replication fork to be defined. The PriA protein plays a key role in this control. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章,评审
doi：10.1016/s1097-2765(03)00110-2
更新日期：2003-03-01 00:00:00
abstract：:Posttranslational modification of proliferating cell nuclear antigen (PCNA), an essential processivity clamp for DNA polymerases, by ubiquitin and SUMO contributes to the coordination of DNA replication, damage tolerance, and mutagenesis. Whereas ubiquitination in response to DNA damage promotes the bypass of replicat...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.06.001
更新日期：2005-07-01 00:00:00
abstract：:The Bloom syndrome helicase BLM and topoisomerase-IIβ-binding protein 1 (TopBP1) are key regulators of genome stability. It was recently proposed that BLM phosphorylation on Ser338 mediates its interaction with TopBP1, to protect BLM from ubiquitylation and degradation (Wang et al., 2013). Here, we show that the BLM-T...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2015.02.012
更新日期：2015-03-19 00:00:00
abstract：:Downstream core promoter elements are an expanding class of regulatory sequences that add considerable diversity to the promoter architecture of RNA polymerase II-transcribed genes. We set out to determine the factors necessary for downstream promoter element (DPE)-dependent transcription and find that, against expect...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.04.005
更新日期：2005-05-13 00:00:00
abstract：:We demonstrate that the major in vivo targets of brefeldin A (BFA) in the secretory pathway of budding yeast are the three members of the Sec7 domain family of ARF exchange factors: Gea1p and Gea2p (functionally interchangeable) and Sec7p. Specific residues within the Sec7 domain are important for BFA inhibition of AR...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80455-4
更新日期：1999-03-01 00:00:00
abstract：:We have used gene competition to distinguish between possible mechanisms of transcriptional activation of the genes of the human beta-globin locus. The insertion of a second beta-globin gene at different points in the locus shows that the more proximal beta gene competes more effectively for activation by the locus co...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80014-3
更新日期：1997-12-01 00:00:00
abstract：:The Mediator complex connects transcriptional activators bound at enhancers with RNA polymerase (Pol) II. demonstrate that Mediator also has an important role in transcriptional activation after recruitment of the Pol II machinery to promoters. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章,评审
doi：10.1016/j.molcel.2005.03.002
更新日期：2005-03-18 00:00:00
abstract：:In a recent issue of Molecular Cell, Shiotani and Zou (2009) elucidate the biochemical mechanism underlying sequential ATM and ATR activation at DNA double-strand breaks, demonstrating that resection transforms ATM substrates into ATR substrates. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2009.03.004
更新日期：2009-03-27 00:00:00
abstract：:Most colorectal cancers (CRCs) containing activated BRAF (BRAF[V600E]) have a CpG island methylator phenotype (CIMP) characterized by aberrant hypermethylation of many genes, including the mismatch repair gene MLH1. MLH1 silencing results in microsatellite instability and a hypermutable phenotype. Through an RNAi scre...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2014.08.010
更新日期：2014-09-18 00:00:00
abstract：:In eukaryotes, a crucial step of translation initiation is the binding of the multifactor complex eIF4F to the 5' end of the mRNA, a prerequisite to recruitment of the activated small ribosomal 43S particle. Histone H4 mRNAs have short 5'UTRs, which do not conform to the conventional scanning-initiation model. Here we...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2010.12.019
更新日期：2011-01-21 00:00:00
abstract：:The functional significance of mono-, di-, and trimethylation of lysine residues within histone proteins remains unclear. Antibodies developed to selectively recognize each of these methylated states at histone H3 lysine 9 (H3 Lys9) demonstrated that mono- and dimethylation localized specifically to silent domains wit...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(03)00479-9
更新日期：2003-12-01 00:00:00
abstract：:Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy res...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2011.06.012
更新日期：2011-07-08 00:00:00
abstract：:Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an add...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.10.012
更新日期：2008-11-07 00:00:00
abstract：:Colicins kill E. coli by a process that involves binding to a surface receptor, entering the cell, and, finally, intoxicating it. The lethal action of colicin E3 is a specific cleavage in the ribosomal decoding A site. The crystal structure of colicin E3, reported here in a binary complex with its immunity protein (IP...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(01)00396-3
更新日期：2001-11-01 00:00:00
abstract：:The heterodimeric nuclear cap binding complex (CBC) binds to 5'-capped polymerase II transcripts. It enhances the efficiency of several mRNA maturation steps and is essential for U snRNA nuclear export in multicellular eukaryotes. The 2A crystal structure of human CBC shows that the large subunit, CBP80, comprises thr...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(01)00299-4
更新日期：2001-08-01 00:00:00
abstract：:B cell CLL/lymphoma-2 (BCL-2) and its relatives comprise the BCL-2 family of proteins, which were originally characterized with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis. Current observations expand BCL-2 family function to include numerous cellular pathways. Here we wi...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2010.01.025
更新日期：2010-02-12 00:00:00
