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RNA Biology

Bappaditya Roy, Qi Liu, Shinichiro Shoji, Kurt Fredrick
Translation begins at AUG, GUG, or UUG codons in bacteria. Start codon recognition occurs in the P site, which may help explain this first-position degeneracy. However, the molecular basis of start codon specificity remains unclear. In this study, we measured the codon dependence of 30S•mRNA•tRNA(fMet) and 30S•mRNA•tRNA(Met) complex formation. We found that complex stability varies over a large range with initiator tRNA(fMet), following the same trend as reported previously for initiation rate in vivo (AUG > GUG, UUG > CUG, AUC, AUA > ACG)...
September 15, 2017: RNA Biology
Kyle Mohler, Rebecca Mann, Amanda Kyle, Noah Reynolds, Michael Ibba
The aminoacylation status of the cellular tRNA pool regulates both general amino acid control (GAAC) and target of rapamycin (TOR) stress response pathways in yeast. Consequently, fidelity of translation at the level of aminoacyl-tRNA synthesis plays a central role in determining accuracy and sensitivity of stress responses. To investigate effects of translational quality control (QC) on cell physiology under stress conditions, phenotypic microarray analyses were used to identify changes in QC deficient cells...
September 14, 2017: RNA Biology
Xiaoling Xu, Huihao Zhou, Quansheng Zhou, Fei Hong, My-Nuong Vo, Wanqiang Niu, Zhiguo Wang, Xiaolin Xiong, Kanaha Nakamura, Keisuke Wakasugi, Paul Schimmel, Xiang-Lei Yang
Tryptophanyl-tRNA synthetase (TrpRS) in vertebrates contains a N-terminal extension in front of the catalytic core. Proteolytic removal of the N-terminal 93 amino acids gives rise to T2-TrpRS, which has potent anti-angiogenic activity mediated through its extracellular interaction with VE-cadherin. Zinc has been shown to have anti-angiogenic effects and can bind to human TrpRS. However, the connection between zinc and the anti-angiogenic function of TrpRS has not been explored. Here we report that zinc binding can induce structural relaxation in human TrpRS to facilitate the proteolytic generation of a T2-TrpRS-like fragment...
September 14, 2017: RNA Biology
Shreya Ahana Ayyub, Divya Dobriyal, Riyaz Ahmad Shah, Kuldeep Lahry, Madhumita Bhattacharyya, Souvik Bhattacharyya, Saikat Chakrabarti, Umesh Varshney
Initiator tRNAs (i-tRNAs) are characterized by the presence of three consecutive GC base pairs (GC/GC/GC) in their anticodon stems in all domains of life. However, many mycoplasmas possess unconventional i-tRNAs wherein the highly conserved sequence of GC/GC/GC is represented by AU/GC/GC, GC/GC/GU or AU/GC/GU. These mycoplasmas also tend to preferentially utilize non-AUG initiation codons. To investigate if initiation with the unconventional i-tRNAs and non-AUG codons in mycoplasmas correlated with the changes in the other components of the translation machinery, we carried out multiple sequence alignments of genes encoding initiation factors (IF), 16S rRNAs, and the ribosomal proteins such as uS9, uS12 and uS13...
September 13, 2017: RNA Biology
Riddhi Desai, Kunmo Kim, Hanna C Buechsenschuetz Allan W Chen, Yumin Bi, Mitchell R Mann, Matthew A Turk, Christina Z Chung, Ilka U Heinemann
tRNA(His) guanylyltransferase (Thg1) has unique reverse (3'-5') polymerase activity occurring in all three domains of life. Most eukaryotic Thg1 homologs are essential genes involved in tRNA(His) maturation. These enzymes normally catalyze a single 5' guanylation of tRNA(His) lacking the essential G(-1) identity element required for aminoacylation. Recent studies suggest that archaeal type Thg1, which includes most archaeal and bacterial Thg1 enzymes is phylogenetically distant from eukaryotic Thg1. Thg1 is evolutionarily related to canonical 5'-3' forward polymerases but catalyzes reverse 3'-5'polymerization...
September 13, 2017: RNA Biology
Aerin Yang, Kyukwang Cho, Hee-Sung Park
Posttranslational modification (PTM) is a key mechanism for regulating diverse protein functions, and thus critically affects many essential biological processes. Critical for systematic study of the effects of PTMs is the ability to obtain recombinant proteins with defined and homogenous modifications. To this end, various synthetic and chemical biology approaches, including genetic code expansion and protein chemical modification methods, have been developed. These methods have proven effective for generating site-specific authentic modifications or structural mimics, and have demonstrated their value for in vitro and in vivo functional studies of diverse PTMs...
September 13, 2017: RNA Biology
Alan C Kessler, Sneha S Kulkarni, Mellie J Paulines, Mary Anne T Rubio, Patrick A Limbach, Zdeněk Paris, Juan D Alfonzo
Retrograde transport of tRNAs from the cytoplasm to the nucleus was first described in Saccharomyces cerevisiae and most recently in mammalian systems. Although the function of retrograde transport is not completely clear, it plays a role in the cellular response to changes in nutrient availability. Under low nutrient conditions tRNAs are sent from the cytoplasm to nucleus and presumably remain in storage there until nutrient levels improve. However, in S. cerevisiae tRNA retrograde transport is constitutive and occurs even when nutrient levels are adequate...
September 13, 2017: RNA Biology
Daniel A Bose, Shelley L Berger
Enhancers are cis- regulatory genetic elements crucial for controlling temporal and cell-type specific patterns of gene expression. Active enhancers generate bi-directional non-coding RNA transcripts called enhancer RNAs (eRNAs). eRNAs are important for stimulating gene expression, but precise mechanisms for this ability remain unclear. Here we highlight recent findings that demonstrate a direct interaction between RNAs and the transcriptional co-activator Creb-binding protein (CBP). Notably, RNA binding could stimulate the core histone acetyltransferase activity of the enzyme, observable in cells as a link between eRNA production, CBP-dependent histone acetylation and expression of genes regulated by specific enhancers...
September 11, 2017: RNA Biology
Àlbert Rafels-Ybern, Adrian Gabriel Torres, Xavier Grau-Bove, Iñaki Ruiz-Trillo, Lluís Ribas de Pouplana
The modification of adenosine to inosine at position 34 of tRNA anticodons has a profound impact upon codon-anticodon recognition. In bacteria, I34 is thought to exist only in tRNA(Arg), while in eukaryotes the modification is present in eight different tRNAs. In eukaryotes, the widespread use of I34 strongly influenced the evolution of genomes in terms of tRNA gene abundance and codon usage. In humans, codon usage indicates that I34 modified tRNAs are preferred for the translation of highly repetitive coding sequences, suggesting that I34 is an important modification for the synthesis of proteins of highly skewed amino acid composition...
September 7, 2017: RNA Biology
Pilar Vazquez-Arango, Dawn O'Reilly
Much evidence is now accumulating that, in addition to their general role in splicing, the components of the core splicing machinery have extensive regulatory potential. In particular, recent evidence has demonstrated that de-regulation of these factors cause the highest extent of alternative splicing changes compared to de-regulation of the classical splicing regulators. This lack of a general inhibition of splicing resonates the differential splicing effects observed in different disease pathologies associated with specific mutations targeting core spliceosomal components...
September 6, 2017: RNA Biology
Maϊwen Caudron-Herger, Sven Diederichs
As a genetic disease, cancer is caused by the activation of oncogenes and the inhibition of tumor suppressor genes via genetic and epigenetic mechanisms. Given the important role of energy metabolism in tumors, we analyzed the cancer-derived mutations occurring in the DNA of the mitochondrion. Mutations in the mitochondrial DNA (mtDNA) compared to nuclear DNA are 62% decreased relative to the coding length per chromosome. We find that the majority of these mutations affects highly conserved nucleotides - significantly exceeding the conservation of the mtDNA - and are devoid of single nucleotide polymorphisms (SNPs)...
September 5, 2017: RNA Biology
Jun Zhou, Youling Fan, Hongtao Chen
The pathogenesis of neuropathic pain (NP) is characterized by an increased responsiveness of nociceptive neurons in the nervous system. However, the molecular mechanisms underpinning the NP still remain elusive. Recent data suggest that long non-coding RNAs (lncRNAs) regulate expression of NP-associated genes. Herein, we analyzed lncRNAs and mRNA profiles in the spinal cord of rats by RNA sequencing during the progression of NP in a spared nerve injury (SNI) model. Sprague-Dawley (SD) rats were employed for the establishment of the SNI models, and nociceptive responses to mechanical and thermal stimuli were measured 3 hours prior to surgery and on postoperative days 1, 3, 7 and 14, with L [4-5] spinal cords extracted from three SD rats under deep anesthesia at each time point after behavioral test...
August 30, 2017: RNA Biology
Alan C Kessler, Gabriel Silveira d'Almeida, Juan D Alfonzo
A signature of most eukaryotic cells is the presence of intricate membrane systems. Intracellular organization presumably evolved to provide order, and add layers for regulation of intracellular processes; compartmentalization also forcibly led to the appearance of sophisticated transport systems. With nucleus-encoded tRNAs, it led to the uncoupling of tRNA synthesis from many of the maturation steps it undergoes. It is now clear that tRNAs are actively transported across intracellular membranes and at any point, in any compartment, they can be post-transcriptionally modified; modification enzymes themselves may localize to any of the genome-containing compartments...
August 29, 2017: RNA Biology
Jeffery M Tharp, Andreas Ehnbom, Wenshe R Liu
Pyrrolysine is the 22(nd) proteinogenic amino acid encoded into proteins in response to amber (TAG) codons in a small number of archaea and bacteria. The incorporation of pyrrolysine is facilitated by a specialized aminoacyl-tRNA synthetase (PylRS) and its cognate tRNA (tRNA(Pyl)). The secondary structure of tRNA(Pyl) contains a number of unique features not found in canonical tRNAs. Numerous studies have demonstrated that the PylRS/tRNA(Pyl) pair from archaea is orthogonal in E. coli and eukaryotic hosts, which has led to the widespread use of this pair for the genetic incorporation of non-canonical amino acids...
August 24, 2017: RNA Biology
Xuejing Zhang, Milton H Hamblin, Ke-Jie Yin
Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest of the transcripts result in RNA transcripts without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members in the lncRNA family, the metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 is one of the first identified lncRNAs associated with human disease, and cumulative studies have indicated that Malat1 plays critical roles in the development and progression of various cancers...
August 24, 2017: RNA Biology
Qi-Lin Zhang, Qian-Hua Zhu, Zheng-Qing Xie, Bin Xu, Xiu-Qiang Wang, Jun-Yuan Chen
Amphioxus is the closest living proxy for exploring the evolutionary origin of the immune system in vertebrates. To understand the immune responses of amphioxus to lipopolysaccharide (LPS), five ribosomal RNA (rRNA)-depleted libraries of amphioxus were constructed, including one control (0 h) library and four treatment libraries at 6, 12, 24, and 48 h post-injection (hpi) with LPS. The transcriptome of Branchiostoma belcheri was analyzed using strand-specific RNA sequencing technology (RNA-seq). A total of 6161, 6665, 7969, and 6447 differentially expressed genes (DEGs) were detected at 6, 12, 24, and 48 hpi, respectively, compared to expression levels at 0 h...
August 24, 2017: RNA Biology
Lumei Liu, Jian Wang, Ramin Khanabdali, Bill Kalionis, Xiantao Tai, Shijin Xia
Circular RNA (circRNA) generated by alternative splicing represents a special class of non-coding RNA molecule. CircRNAs are abundant in the eukaryotic cell cytoplasm and have a characteristic organization, timing of action and disease specificity. In contrast to linear RNA, circRNAs are resistant to RNA exonuclease. Consequently, circRNA escapes normal RNA turnover and this improves circRNA stability. CircRNAs can be degraded by microRNA (miRNA) and this results in linearization of the circRNA, which can then act as competitor to endogenous RNA...
August 18, 2017: RNA Biology
Andreas Keller, Trine Rounge, Christina Backes, Nicole Ludwig, Randi Gislefoss, Petra Leidinger, Hilde Langseth, Eckart Meese
An increasing number of studies propose circulating microRNAs (miRNAs) as biomarkers for a large number of human diseases including cancer, cardiovascular diseases, neurological pathologies and others. To further validate miRNA as biomarkers it is indispensable to understand the variability of circulating miRNAs in healthy individuals. We determined the longitudinal miRNomes of 90 serum samples from the Janus Serum Bank in Norway, which have been stored between 23 and 40 years at -25 degrees Celsius. We profiled three serum samples with microarrays for 30 individuals, each...
August 18, 2017: RNA Biology
Vasili Hauryliuk, Gemma C Atkinson
The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, antibiotic tolerance and pathogenicity. We have recently shown that the Small Alarmone Synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis has an RNA-binding activity (Beljantseva et al. 2017). RelQ's activities as an enzyme and as a RNA-binding protein are mutually incompatible: binding of single-stranded RNA potently inhibits (p)ppGpp synthesis in a sequence-specific manner, and RelQ's enzymatic activity destabilizes the RNA:RelQ complex...
August 18, 2017: RNA Biology
Nabeel S Ganem, Ayelet T Lamm
Adenosine-to-inosine RNA editing is a conserved process, which is performed by ADAR enzymes. By changing nucleotides in coding regions of genes and altering codons, ADARs expand the cell's protein repertoire. This function of the ADAR enzymes is essential for human brain development. However, most of the known editing sites are in non-coding repetitive regions in the transcriptome and the purpose of editing in these regions is unclear. Recent studies, which have shown that editing levels of transcripts vary between tissues and developmental stages in many organisms, suggest that the targeted RNA and ADAR editing are both regulated...
August 18, 2017: RNA Biology
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