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RNA Biology

Etienne B Greenlee, Shira Stav, Ruben M Atilho, Kenneth I Brewer, Kimberly A Harris, Sarah N Malkowski, Gayan Mirihana Arachchilage, Kevin R Perkins, Madeline E Sherlock, Ronald R Breaker
Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn(2+), and the metabolites guanidine and PRPP...
November 14, 2017: RNA Biology
Kelly T Hughes, Fabienne F V Chevance
A complex process translates messenger RNA (mRNA) base sequence into protein amino acid sequence. Transfer RNAs must recognize 3-base codons in the mRNA to insert the correct amino acids into the growing protein. Codon degeneracy makes decoding complicated in that multiple (synonymous) triplets can encode a single amino acid and multiple tRNAs can have the same anticodon. Over the last twenty years, new developments in structural biology, genome sequencing and bioinformatics has elucidated the intricacies of the ribosome structure and the details of the translation process...
November 13, 2017: RNA Biology
German Martinez
Previously believed to be mere random degradation products, tRNA-derived small RNAs have been lately connected to a series of functions that include, surprisingly, genome protection against retrotransposons. tRNAs have been known for a long time to be involved in the replication cycle of retroviruses, pararetroviruses and retrotransposons as primers of their reverse transcription. tRNA-derived small RNAs, as functional small RNAs or as mere tRNA degradation products, have emerged as important players in the regulation of genic transcription...
November 9, 2017: RNA Biology
Katherine McJunkin
The window of embryonic development after fertilization but prior to the beginning of transcription from the zygotic genome is a period that relies heavily on post-transcriptional regulation of gene expression. MicroRNAs constitute one of the predominant mechanisms of post-transcriptional gene regulation, yet their biological function and molecular mechanism of action during this developmental window is poorly understood. Our recent findings demonstrate that the maternal contribution of mir-35 family members contributes to zygotic developmental decisions (sex determination) in C...
November 9, 2017: RNA Biology
Michael J Ellis, Lindsey A Carfrae, Craig R Macnair, Ryan S Trussler, Eric D Brown, David B Haniford
Bacterial transposons were long thought of as selfish mobile genetic elements that propagate at the expense of 'host' bacterium fitness. However, limited transposition can benefit the host organism by promoting DNA rearrangements and facilitating horizontal gene transfer. Here we discuss and provide context for our recently published work which reported the surprising finding that an otherwise dormant transposon, IS200, encodes a regulatory RNA in Salmonella Typhimurium. This previous work identified a trans-acting sRNA that is encoded in the 5'UTR of IS200 transposase mRNA (tnpA)...
November 9, 2017: RNA Biology
Lena A Wurmthaler, Benedikt Klauser, Jörg S Hartig
Recent bioinformatics studies have demonstrated a wide-spread occurrence of the hammerhead ribozyme (HHR) and similar small endonucleolytic RNA motifs in all domains of life. It is becoming increasingly evident that such ribozyme motifs participate in important genetic processes in diverse organisms. Although the HHR motif has been studied for more than three decades, only little is known about the consequences of ribozyme activity on gene expression. In the present study we analysed eight different naturally occurring HHR sequences in diverse genetic and organismal contexts...
November 6, 2017: RNA Biology
Gayan Mirihana Arachchilage, Madeline E Sherlock, Zasha Weinberg, Ronald R Breaker
Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species...
November 6, 2017: RNA Biology
Laurence Van Melderen, Dukas Jurenas, Abel Garcia-Pino
Toxin---antitoxin systems (TA) are widespread in bacteria and archea. They are commonly found in chromosomes and mobile genetic elements. These systems move from different genomic locations and bacterial hosts through horizontal gene transfer, using mobile elements as vehicles. Their potential roles in bacterial physiology are still a matter of debate in the field. The mechanisms of action of different toxin families have been deciphered at the molecular level. Intriguingly, the vast majority of these toxins target protein synthesis...
November 3, 2017: RNA Biology
Joanna Sztuba-Solinska, Stuart F J Le Grice
As the notion of small molecule targeting of regulatory viral and cellular RNAs gathers momentum, understanding their structure, and variations thereof, in the appropriate biological context will play a critical role. This is especially true of the ∼1100-nt polyadenylated nuclear (PAN) long non-coding (lnc) RNA of Kaposi's sarcoma herpesvirus (KSHV), whose interaction with viral and cellular proteins is central to lytic infection. Nuclear accumulation of PAN RNA is mediated via a unique triple helical structure at its 3' terminus (within the expression and nuclear retention element, or ENE) which protects it from deadenylation-dependent decay...
November 3, 2017: RNA Biology
Felix G M Ernst, Lieselotte Erber, Joana Sammler, Frank Jühling, Heike Betat, Mario Mörl
Cold adaptation is an evolutionary process that has dramatic impact on enzymatic activity. Increased flexibility of the protein structure represents the main evolutionary strategy for efficient catalysis and reaction rates in the cold, but is achieved at the expense of structural stability. This results in a significant activity-stability tradeoff, as it was observed for several metabolic enzymes. In polymerases, however, not only reaction rates, but also fidelity plays an important role, as these enzymes have to synthesize copies of DNA and RNA as exact as possible...
November 3, 2017: RNA Biology
Amita Barik, Santasabuj Das
Small RNAs (sRNAs) in bacteria have emerged as key players in transcriptional and post-transcriptional regulation of gene expression. Here, we present a statistical analysis of different sequence- and structure-related features of bacterial sRNAs to identify the descriptors that could discriminate sRNAs from other bacterial RNAs. We investigated a comprehensive and heterogeneous collection of 816 sRNAs, identified by northern blotting across 33 bacterial species and compared their various features with other classes of bacterial RNAs, such as tRNAs, rRNAs and mRNAs...
November 3, 2017: RNA Biology
Sarah Catherine Mills, Ramya Enganti, Albrecht G von Arnim
In most organisms gene expression over the course of the day is under the control of the circadian clock. The canonical clock operates as a gene expression circuit that is controlled at the level of transcription, and transcriptional control is also a major clock output. However, rhythmic transcription cannot explain all the observed rhythms in protein accumulation. Although it is clear that rhythmic gene expression also involves RNA processing and protein turnover, until two years ago little was known in any eukaryote about diel dynamics of mRNA translation into protein...
November 3, 2017: RNA Biology
Andreia Gomes-Duarte, Rafaela Lacerda, Juliane Menezes, Luísa Romão
The eukaryotic initiation factor 3 (eIF3) is one of the most complex translation initiation factors in mammalian cells, consisting of several subunits (eIF3a to eIF3m). It is crucial in translation initiation and termination, and in ribosomal recycling. Accordingly, deregulated eIF3 expression is associated with different pathological conditions, including cancer. In this manuscript, we discuss the interactome and function of each subunit of the human eIF3 complex. Furthermore, we review how altered levels of eIF3 subunits correlate with neurodegenerative disorders and cancer onset and development; in addition, we evaluate how such misregulation may also trigger infection cascades...
November 3, 2017: RNA Biology
Bonnie J Cuthbert, Kalistyn H Burley, Celia W Goulding
Bovine pancreatic ribonuclease (RNase A) is the founding member of the RNase A superfamily. Members of this superfamily of ribonucleases have high sequence diversity, but possess a similar structural fold, together with a conserved His-Lys-His catalytic triad and structural disulfide bonds. Until recently, RNase A proteins had exclusively been identified in eukaryotes within vertebrae. Here, we discuss the discovery by Batot et al. of a bacterial RNase A superfamily member, CdiA-CT(Ykris): a toxin that belongs to an inter-bacterial competition system from Yersinia kristensenii...
November 3, 2017: RNA Biology
Isabel C Vallecillo-Viejo, Noa Liscovitch-Brauer, Maria Fernanda Montiel-Gonzalez, Eli Eisenberg, Joshua J C Rosenthal
Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells...
November 3, 2017: RNA Biology
Hassaan Mehboob Awan, Abdullah Shah, Farooq Rashid, Shuai Wei, Liang Chen, Ge Shan
microRNAs (miRNAs) are critical regulators of gene expression. For elucidating functional roles of miRNAs, it is critical to identify their direct targets. There are debates about whether pulldown of biotinylated miRNA mimics can be used to identify miRNA targets or not. Here we show that biotin-labelled miR-34a can be loaded to AGO2, and AGO2 immunoprecipitation can pulldown biotinylated miR-34a (Bio-miR pulldown). RNA-sequencing (RNA-seq) of the Bio-miR pulldown RNAs efficiently identified miR-34a mRNA targets, which could be verified with luciferase assays...
October 13, 2017: RNA Biology
Jie Yang, Xiaodan Meng, Jinchang Pan, Nan Jiang, Chengwei Zhou, Zhenhua Wu, Zhaohui Gong
Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system...
October 13, 2017: RNA Biology
Florian Hinze, Philipp Drewe-Boß, Miha Milek, Uwe Ohler, Markus Landthaler, Michael Gotthardt
PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation) facilitates the identification and mapping of protein/RNA interactions. So far, it has been limited to select cell-lines as it requires efficient 4SU uptake. To increase transcriptome complexity and thus identify additional RNA-protein interaction sites we fused HEK 293 T-Rex cells (HEK293-Y) that express the RNA binding protein YBX1 with PC12 cells expressing eGFP (PC12-eGFP). The resulting hybrids enable PAR-CLIP on a neuronally expanded transcriptome (Fusion-CLIP) and serve as a proof of principle...
October 13, 2017: RNA Biology
Yaseswini Neelamraju, Abel Gonzalez-Perez, Poornima Bhat-Nakshatri, Harikrishna Nakshatri, Sarath Chandra Janga
RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations...
October 12, 2017: RNA Biology
Jayanti Jodder, Rohit Das, Deepti Sarkar, Payel Bhattacharjee, Pallob Kundu
Besides their definite role in plant developmental processes miR167 also serve as mediator of stress response. Although differential expression of miR167 occurs during stresses, the regulatory-mechanism of biogenesis remained elusive. Therefore, using tomato as the model plant we have explored the mechanism of regulation of miR167a expression during stresses. Fungus or virus infections and exposure to cold stress raised the level of miR167a expression. Whereas, salt, drought and heat treatments resulted in the downregulation, indicating different stresses activated alternative mechanisms for miR167a regulation...
October 12, 2017: RNA Biology
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