Abstract:
:Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Guiducci G,Paone A,Tramonti A,Giardina G,Rinaldo S,Bouzidi A,Magnifico MC,Marani M,Menendez JA,Fatica A,Macone A,Armaos A,Tartaglia GG,Contestabile R,Paiardini A,Cutruzzolà Fdoi
10.1093/nar/gkz129subject
Has Abstractpub_date
2019-05-07 00:00:00pages
4240-4254issue
8eissn
0305-1048issn
1362-4962pii
5365575journal_volume
47pub_type
杂志文章abstract::Directed molecular evolution and combinatorial methodologies are playing an increasingly important role in the field of protein engineering. The general approach of generating a library of partially randomized genes, expressing the gene library to generate the proteins the library encodes and then screening the protei...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkh315
更新日期:2004-02-27 00:00:00
abstract::Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks169
更新日期:2012-06-01 00:00:00
abstract::The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking we demonstrate here tha...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv312
更新日期:2015-05-19 00:00:00
abstract::The thermal denaturation spectra of E. coli 50s and 30s ribosomal sub units and of their isolated RNA's were studied over the wavelength range of 2300-3000 Angstrom. It was possible to fit the experimental denaturation spectra with super positions of the reference spectra for denaturation of A - U and G - C base pairs...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/2.3.373
更新日期:1975-03-01 00:00:00
abstract::Fluorogenic RNAs that are based on the complex formed by 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI) derivatives and the RNA aptamer named Spinach were used to engineer a new generation of in vitro and in vivo sensors for bioanalytics. With the resolved crystal structure of the RNA/small molecule complex, ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv944
更新日期:2015-10-30 00:00:00
abstract::Targeted genome engineering requires nucleases that introduce a highly specific double-strand break in the genome that is either processed by homology-directed repair in the presence of a homologous repair template or by non-homologous end-joining (NHEJ) that usually results in insertions or deletions. The error-prone...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt080
更新日期:2013-04-01 00:00:00
abstract::Multiplexed high-throughput pyrosequencing is currently limited in complexity (number of samples sequenced in parallel), and in capacity (number of sequences obtained per sample). Physical-space segregation of the sequencing platform into a fixed number of channels allows limited multiplexing, but obscures available s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm760
更新日期:2007-01-01 00:00:00
abstract::The nucleolus is a unique structural component of interphase nuclei where the ribosomal genes, trans-cribed by RNA polymerase I (RNA pol I), are organized. In the present study, the repair of UV-induced photolesions was investigated in the ribosomal DNA (rDNA) in relation to RNA pol I transcription. We used hamster ce...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.12.2511
更新日期:1999-06-15 00:00:00
abstract::Restriction fragment patterns of G+C-rich satellites of sheep and goat DNA were compared. The 1,712 g/cm3 satellites of both species appear homologous, consisting of repeats 760 base pairs long and showing coincidence of position of primary+ EcoRI, BamHI and most BspRI restriction target sites. The EcoRI and BamHI end...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.1.57
更新日期:1979-01-01 00:00:00
abstract::NMR methods were used to investigate a series of mutants of the pseudoknot within the gene 32 messenger RNA of bacteriophage T2, for the purpose of investigating the range of sequences, stem and loop lengths that can form a similar pseudoknot structure. This information is of particular relevance since the T2 pseudokn...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.6.1130
更新日期:1997-03-15 00:00:00
abstract::Yeast tRNA Lys2 codes preferentially for AAA and contains a 2-thiouridine derivative (U) at the 5'-position of the anticodon. Removal of the 2-thio group from U by treatment with CNBr did not affect the amino acid accepting activity of the modified tRNA Lys2. CNBr treated tRNA Lys2 was active in protein synthesis but ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.3.523
更新日期:1976-03-01 00:00:00
abstract::Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have establish...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky171
更新日期:2018-05-18 00:00:00
abstract::In 4M NaCl solutions (dC-dG)n (n = 3,4; approximately 9 mM) exist as a mixture o +/- B and Z forms. The low and high field components of two 31P NMR resonances originating from internal phosphodiester groups are assigned to the GpC and CpG linkages, respectively. Low temperatures stabilize the Z-forms, which completel...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.11.4625
更新日期:1984-06-11 00:00:00
abstract::The 5'-cap of spliceosomal small nuclear RNAs, some small nucleolar RNAs and of telomerase RNA was found to be hypermethylated in vivo. The Trimethylguanosine Synthase 1 (TGS1) mediates this conversion of the 7-methylguanosine-cap to the 2,2,7-trimethylguanosine (m(3)G)-cap during maturation of the RNPs. For mammalian...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp249
更新日期:2009-07-01 00:00:00
abstract::Single cell RNA-seq experiments provide valuable insight into cellular heterogeneity but suffer from low coverage, 3' bias and technical noise. These unique properties of single cell RNA-seq data make study of alternative splicing difficult, and thus most single cell studies have restricted analysis of transcriptome v...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1525
更新日期:2016-05-05 00:00:00
abstract::The repAC operon of plasmid RSF1010 consists of the genes for proteins E, F, RepA (DNA helicase), and RepC (origin-binding initiator protein) and is transcriptionally initiated by a promoter called P4. We have studied the expression of the repAC operon in vivo by using fusions to the lacZ reporter gene. The results sh...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.21.6215
更新日期:1990-11-11 00:00:00
abstract::The effect of amino groups attached at positions 2 and 8 of the hypoxanthine moiety in the structure, reactivity and stability of DNA duplexes and triplexes is studied by means of quantum mechanical calculations, as well as extended molecular dynamics (MD) and thermodynamic integration (MD/TI) simulations. Theoretical...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.12.2522
更新日期:2001-06-15 00:00:00
abstract::Archival formalin-fixed, paraffin-embedded and ethanol-fixed tissues represent a potentially invaluable resource for gene expression analysis, as they are the most widely available material for studies of human disease. Little data are available evaluating whether RNA obtained from fixed (archival) tissues could produ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.2.e4
更新日期:2002-01-15 00:00:00
abstract::Guanine-rich DNA sequences can form G-quadruplexes stabilized by stacked G-G-G-G tetrads in monovalent cation-containing solution. The length and number of individual G-tracts and the length and sequence context of linker residues define the diverse topologies adopted by G-quadruplexes. The review highlights recent so...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkm711
更新日期:2007-01-01 00:00:00
abstract::Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1254
更新日期:2017-03-17 00:00:00
abstract::The Diatom Expressed Sequence Tag (EST) Database was constructed to provide integral access to ESTs from these ecologically and evolutionarily interesting microalgae. It has now been updated with 130,000 Phaeodactylum tricornutum ESTs from 16 cDNA libraries and 77,000 Thalassiosira pseudonana ESTs from seven libraries...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn905
更新日期:2009-01-01 00:00:00
abstract::Small RNA (sRNA) Sequencing technology has revealed that microRNAs (miRNAs) are capable of exhibiting frequent variations from their canonical sequences, generating multiple variants: the isoforms of miRNAs (isomiRs). However, integrated tool to precisely detect and systematically annotate isomiRs from sRNA sequencing...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw427
更新日期:2016-07-08 00:00:00
abstract::GenBank is a comprehensive database that contains publicly available DNA sequences for more than 140 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the BankIt (web) or Sequin program an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh045
更新日期:2004-01-01 00:00:00
abstract::Calf lens messenger fractions have been purified on poly(dT)-cellulose. The purified RNA's have been analyzed as nucleosides by a method which can be used on a micro-scale with highly reproduceble results. Both the 10S and 14S lens mRNA contain poly A sequences. The poly A content found in 14S mRNA cannot account for ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/1.2.245
更新日期:1974-02-01 00:00:00
abstract::Dimerization of HIV-1 genomic RNA is an essential step of the viral cycle, initiated at a conserved stem-loop structure which forms a 'kissing complex' involving loop-loop interactions (dimerization initiation site, DIS). A 19mer RNA oligonucleotide (DIS-19) has been synthesized which forms a stable symmetrical dimer ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.15.3567
更新日期:1998-08-01 00:00:00
abstract::Sae2 cooperates with the Mre11-Rad50-Xrs2 (MRX) complex to initiate resection of DNA double-strand breaks (DSBs) and to maintain the DSB ends in close proximity to allow their repair. How these diverse MRX-Sae2 functions contribute to DNA damage resistance is not known. Here, we describe mre11 alleles that suppress th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky086
更新日期:2018-04-06 00:00:00
abstract::The sequence of 436 nucleotides around the region coding for 5.8S RNA in the Sciara coprophila rDNA transcription unit (1) has been determined. Regions coding for 5.8S and 2S RNAs have been identified; they are 80 - 90% homologous to the corresponding Drosophila sequences and are separated by a 22 nucleotide long spac...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/8.16.3565
更新日期:1980-08-25 00:00:00
abstract::We have isolated the mouse MyoD1 gene flanked by its promoter region by screening a genomic library with synthetic oligonucleotides. The structural gene is interrupted by two G + C rich introns. Transfection of the cloned gene inserted into an expression vector converts fibroblasts to myoblasts. Sequence analysis of a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.23.6433
更新日期:1991-12-11 00:00:00
abstract::Novel techniques for high-throughput steady-state metabolomic profiling yield information about changes of nearly thousands of metabolites. Such metabolomic profiles, when analyzed together with transcriptional profiles, can reveal novel insights about underlying biological processes. While a number of conceptual appr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw266
更新日期:2016-07-08 00:00:00
abstract::A newly designed cyclic bis-naphthyridine carbamate dimer CMBL4: with a limited conformational flexibility was synthesized and characterized. Absorption spectra revealed that two naphthyridines in CMBL4: were stacked on each other in aqueous solutions. The most efficient binding of CMBL4: to DNA was observed for the s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw672
更新日期:2016-09-06 00:00:00