Feed43 : Convert any web page to news feed on the fly. Feed43 : Convert any web page to news feed on the fly. Feed43 : Convert any web page to news feed on the fly. Aminoacylating Urzymes Challenge the RNA World Hypothesis. + Author Affiliations ↵1 To whom correspondence should be addressed: Dept. of Biochemistry and Biophysics, CB 7260, University of North Carolina, Chapel Hill, NC 27599-7260. Tel.: 919-966-3263; Fax: 919-966-2852; E-mail: carter@med.unc.edu. Capsule Background: RNA World scenarios require high initial fidelity, greatly slowing lift-off. Results: Class I TrpRS and Class II HisRS Urzymes (120–130 residues) both acylate tRNAs ∼106 times faster than the uncatalyzed peptide synthesis rate.
Conclusion: Urzymes appear highly evolved, implying that they had even simpler ancestors. Significance: High Urzyme catalytic proficiencies imply that translation began in a Peptide·RNA World. Abstract We describe experimental evidence that ancestral peptide catalysts substantially accelerated development of genetic coding. Footnotes ↵* This work was supported by NIGMS/National Institutes of Health Grants 78227 (to C. Feed43 : Convert any web page to news feed on the fly.
Feed43 : Convert any web page to news feed on the fly. Convert any web page to news feed on the fly. The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO) Genome-wide identification and quantitative analysis of cleaved tRNA fragments induced by cellular stress. + Author Affiliations ↵* Corresponding author; email: mxh8@case.edu Capsule Background: Regulation of stress-induced tRNA cleavage by angiogenin is not well studied.
Results: tRNA fragment accumulation was higher during oxidative than hypertonic stress. Conclusion: tRNA cleavage is regulated by the availability of angiogenin and tRNA substrate, levels of RNH1 and the rates of protein synthesis. Significance: Stress-specific tRNA cleavage mechanisms and patterns will provide insights into novel stress signaling pathways. Abstract Certain stress conditions can induce cleavage of tRNAs around the anticodon loop via the use of the ribonuclease angiogenin. 4-demethylwyosine synthase from Pyrococcus abyssi is a Radical-SAM enzyme with an additional [4Fe-4S]+2 cluster which interacts with the pyruvate co-substrate. + Author Affiliations ↵* Corresponding author; email: mohamed.atta@cea.fr Capsule Background: 4-demethylwyosine synthase (TYW1) is a tRNA-modifying metalloenzyme involved in the biosynthesis of Wyosine.
Results: TYW1 enzyme belongs to the Radical-SAM superfamily with two Fe-S clusters involved in catalysis. Conclusion: The canonical Radical-SAM cluster binds and activates SAM co-factor while the additional [4Fe-4S] cluster is shown to interact with the pyruvate co-substrate. Significance: This study helps to understand how radical-SAM enzymes with two Fe-S centers achieve radical insertion reactions. Abstract Wybutosine (yW) and its derivatives are found in position 37 of tRNA encoding Phe in eukaryotes and archaea. Oligonucleotide models of telomeric DNA and RNA form a hybrid G-quadruplex structure as a potential component of telomeres.
Capsule Background: Telomeric repeat-containing RNA has recently been found in mammalian cells. Results: Oligonucleotide models of telomeric DNA and RNA form a hybrid G-quadruplex structure. Conclusion: We suggest a model system for understanding the structure and function of human telomeres. Significance: Our finding provides valuable information for understanding the structure and function of human telomere DNA and RNA. Abstract Telomeric repeat-containing RNA, a non-coding RNA molecule, has recently been found in mammalian cells. Life in a three-dimensional grid. Yeast ribosomal protein L40 assembles late into pre-60S ribosomes and is required for their cytoplasmic maturation. Capsule Background: The contribution of ribosomal proteins to ribosome assembly and function is often not well understood. Results: L40 assembles within the cytoplasm into pre-60S subunits and is required for Nmd3 and Rlp24 recycling. Conclusion: L40 contributes to formation of 60S subunits competent for subunit joining and translation elongation.
Significance: Our analysis of L40 function reveals an additional step during cytoplasmic pre-60S maturation events. Abstract Most ribosomal proteins play important roles in ribosome biogenesis and function. The selenocysteine-specific elongation factor contains a novel and multi-functional domain. Capsule Background: Selenocysteine incorporation requires the function of a unique translation elongation factor, eEFSec. Results: The novel Domain IV of eEFSec is required for at least three functions. Conclusion: Domain IV of eEFSec is the key site for dictating specificity in the conversion of the UGA stop codon into a Sec codon.
Significance: Understanding elongation factor function is critical to deciphering the mechanism of Sec incorporation. Abstract The Sec-specific elongation factor eEFSec delivers the aminoacylated selenocysteine-tRNA (Sec-tRNASec) to the ribosome and suppresses UGA codons that are upstream of Sec Insertion Sequence (SECIS) elements bound by SECIS binding protein 2 (SBP2). Global Identification of New Substrates for the Yeast Endoribonuclease, RNase Mitochondrial RNA Processing (MRP) Capsule Background: A global RNase MRP substrate hunt has never been performed. Results: We identified new potential substrates for RNase MRP. Conclusion: Results confirm a role for RNase MRP in cell cycle and identify new roles in the biosynthesis of other RNA/protein complexes. Significance: Knowing the identity of RNase MRP substrates is critical to understanding its function and role on a system-wide scale. Abstract RNase MRP is an essential, evolutionarily conserved endoribonuclease composed of 10 different protein subunits and a single RNA.
Snail Represses the Splicing Regulator ESRP1 to Promote Epithelial-Mesenchymal Transition. Capsule Background: The splicing regulator ESRP1 prevents CD44 splice isoform switching during epithelial-mesenchymal transition (EMT), a developmental process frequently reactivated in cancer progression. Results: Snail represses ESRP1 transcription, thus promoting CD44 isoform switching during EMT. Conclusion: Snail′s repression of ESRP1 transcription is required for EMT to occur. Significance: Investigating mechanisms that regulate alternative splicing during EMT will facilitate our understanding of the EMT associated with cancer recurrence and metastasis.
Abstract Epithelial-mesenchymal transition (EMT), a tightly regulated process that is critical for development, is frequently re-activated during cancer metastasis and recurrence. Received July 1, 2012. Human Pumilio proteins recruit multiple deadenylases to efficiently repress messenger RNAs. + Author Affiliations ↵* Corresponding author; email: acgold@umich.edu Capsule Background: The mechanisms by which human PUF proteins repress target mRNAs remain unknown.
Results: PUM1 and PUM2 reduce protein and mRNA levels of targets by recruiting the CNOT deadenylase complex and by a poly(A)-independent mechanism. Conclusion: PUMs employ deadenylation-dependent and independent mechanisms of repression. Significance: Deadenylation is a conserved means of PUF repression but additional mechanism(s) contribute to mRNA regulation. Abstract PUF proteins are a conserved family of eukaryotic RNA binding proteins that regulate specific mRNAs: they control many processes including stem cell proliferation, fertility and memory formation. Identical RNA-protein interactions in vivo & in vitro and a scheme of folding the newly synthesized proteins by ribosomes. + Author Affiliations ↵* Corresponding author; email: chanchaldg2000@yahoo.com Capsule Background: Ribosomal PTC acts as protein folding modulator in vivo and in vitro.
Results: A fixed set of nucleotides in the PTC interact to fold polypeptides in vivo and in vitro. Conclusion: Folding all proteins through interaction with the same set of nucleotides in PTC implies an intrinsic homology in them. Significance: Hundreds of proteins showed identical cumulative hydrophobicity plot for amino acids. Abstract Distinct three dimensional shape of rRNA inside the ribosome is required for the peptidyl transfer activity of its peptidyl transferase center (PTC). dTIS11-dependent polysomal deadenylation is the key step in AU-Rich Element-mediated mRNA decay in Drosophila cells. Capsule Background: TIS11 proteins control the degradation of mRNA containing AU-Rich Elements (ARE).
Results: Drosophila dTIS11 activates the polysomal deadenylation of the ARE mRNA Cecropin A1. Conclusion: Drosophila dTIS11 controls fewer aspects of ARE mRNA decay as compared to its mammalian homologs. Significance: TIS11 proteins may have acquired additional functions to control mRNA decay during evolution from invertebrates to mammals. Abstract The destabilization of AU-Rich Element (ARE)-containing mRNAs mediated by proteins of the TIS11 family is conserved among eukaryotes including Drosophila. Dephosphorylation of HuR Protein During Alphavirus Infection Is Associated with HuR Relocalization to the Cytoplasm. + Author Affiliations ↵* Corresponding author; email: jeffrey.wilusz@colostate.edu Capsule Background: Sindbis virus RNAs bind the cellular HuR protein and cause its relocalization to the cytoplasm.
Results: HuR relocalization occurs with other alphaviruses but not with several unrelated RNA viruses; it is associated with altered protein phosphorylation. Conclusion: HuR relocalization is alphavirus-selective and appears to be distinct from other types of HuR shuttling. Significance: This has potential therapeutic and diagnostic implications for alphavirus infections. Abstract We have previously demonstrated that the cellular HuR protein binds U-rich elements in the 3-primeUTR of Sindbis virus RNA and relocalizes from the nucleus to the cytoplasm upon Sindbis virus infection in 293T cells. Biosynthesis of 4-thiouridine in tRNA in the methanogenic archaeon Methanococcus maripaludis. Capsule Background: Bacterial ThiI catalyzes 4-thiouridine biosynthesis by using a rhodanese-like domain for sulfur transfer. Results: ThiI in methanogenic archaea employs a conserved CXXC motif to generate persulfide and disulfide intermediates for sulfur transfer. Conclusion: Methanogens possess a unique sulfur relay strategy.
Significance: Sulfur metabolism in methanogens is a model for the evolution of sulfur metabolism in the anaerobic, sulfide-rich environments common on ancient earth. Abstract 4-Thiouridine (s4U) is a conserved modified nucleotide in position 8 of bacterial and archaeal tRNAs and plays a role in protecting cells from near-UV killing. Escherichia coli employs two enzymes for its synthesis: the cysteine desulfurase IscS, which forms a Cys persulfide enzyme adduct from free Cys, and ThiI, which adenylates U8 and transfers sulfur from IscS to form s4U.
Exoribonuclease and Endoribonuclease Activities of RNase BN/RNase Z Both Function In Vivo. Capsule Background: In contrast to other RNase Z endoribonucleases, RNase BN is also an exoribonuclease in vitro. Results: Cells dependent on RNase BN for growth are affected by a single amino acid change that eliminates exoribonuclease activity. Conclusion: In addition to its endoribonuclease activity, the exoribonuclease of RNase BN also can participate in tRNA maturation. Significance: RNase BN can serve as a dual-function nuclease in vivo. Abstract Escherichia coli RNase BN, a member of the RNase Z family of endoribonucleases, differs from other family members in that it also can act as an exoribonuclease in vitro. TmRNA-SmpB regulates RNase R turnover by promoting binding of HslUV and Lon proteases. Capsule Background: RNase R is unstable due to its acetylation and resulting binding of tmRNA-SmpB, but is stabilized under stress conditions.
Results: tmRNA-SmpB promotes RNase R proteolysis by stimulating binding of Lon and HslUV. Conclusion: Acetylation initiates a series of events ultimately leading to RNase R proteolysis. Significance: This work elucidates a novel regulatory mechanism previously unknown in bacteria. Abstract RNase R, an important exoribonuclease involved in degradation of structured RNA, is subject to a novel mechanism of regulation. The enzyme is extremely unstable in rapidly-growing cells, but becomes stabilized under conditions of stress, such as stationary phase or cold shock. Phosphoregulation of the RNA-binding protein HuR by CDK5 Affects Centrosome Function.
Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression. Arabidopsis molybdopterin biosynthesis protein Cnx5 collaborates with the ubiquitin-like protein Urm11 in the thio-modification of tRNA. Correlation Between NS5A Dimerization and HCV replication. Growth of a Bacterium that Apparently Uses Arsenic Instead of Phosphorus is a Consequence of Massive Ribosome Breakdown.
Proteobacterial ArfA peptides are synthesized from non-stop messenger RNAs. APOBEC3G Inhibits MicroRNA-mediated Repression of Translation by Interfering with the Interaction between Argonaute-2 and MOV10. A retroelement modifies pre-mRNA splicing: The murine Glrbspa allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion. Inhibition of pokeweed antiviral protein (PAP) by turnip mosaic virus genome-linked protein (VPg) The mechanism of pre-transfer editing in yeast mitochondrial threonyl-tRNA synthetase.
An archaeal immune system can detect multiple protospacer adjacent motifs (PAMs) to target invader DNA. Dual-specificity-tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A ) modulates serine-arginine rich protein 55 (SRp55)-promoted tau exon 10 inclusion. Expression of provirus integration site for Moloney murine leukemia virus 1 is post-transcriptionally regulated by tristetraprolin in cancer cells. The DEAD-box RNA Helicase Dbp2 Connects RNA Quality Control with Repression of Aberrant Transcription. The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis. The protein Zfand5 binds and stabilizes mRNAs with AU-rich elements in their 3 primeuntranslated regions. Trypanosoma brucei 20S editosomes have one RNA substrate-binding site and execute RNA unwinding activity. A novel one-step mechanism for tRNA 3' end maturation by the exoribonuclease RNase R of Mycoplasma genitalium.
Micro RNAs in the pineal gland: mir-483 regulates melatonin synthesis by targeting arylalkylamine N-Acetyltransferase. A conserved serine of heterogeneous nuclear ribonucleoprotein L (hnRNP L) mediates depolarization-regulated alternative splicing of potassium channels. Yar1 protects the ribosomal protein Rps3 from aggregation. MicroRNA-148a promotes myogenic differentiation by targeting the ROCK1 gene. Riboswitch (T-Box)-mediated control of tRNA-dependent amidation in clostridium acetobutylicum rationalizes gene and pathway redundancy for asparagine and asparaginyl-tRNAAsn synthesis.
The structurally conserved Nop56/58 N-terminal domain facilitates archaeal box C/D sRNP-guided methyltransferase activity. A conserved interface between PUF and CPEB proteins.