scholarly journals The Reading Frame Surveillance Hypothesis

2016 ◽  
Author(s):  
John T. Gray
Keyword(s):  
Large Subunit ◽  
Protein Translation ◽  
Small Subunit ◽  
Phenotypic Traits ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Reading Frame ◽  
Mammalian Sperm ◽  
Translation Mechanism

AbbreviationsRFSReading Frame SurveillanceRdRPRNA-dependent RNA PolymerasefrRNAsFraming RNAsLSULarge SubunitSSUSmall SubunittRFTransfer RNA derived FragmentntnucleotideAbstractAn alternative model for protein translation is presented wherein ribosomes utilize a complementary RNA copy of protein coding sequences to monitor the progress of messenger RNAs during their translation to reduce the frequency of frameshifting errors. The synthesis of this ‘framing RNA’ is postulated to be catalyzed by the small subunit of the ribosome, in the decoding center, by excising and concatemerizing tRNA anticodons bound to each codon of the mRNA template. Various components of the model are supported by previous observations of tRNA mutants that impact ribosomal frameshifting, unique globin-coding RNAs in developing erythroblasts, and the epigenetic, intergenerational transfer of phenotypic traits via mammalian sperm RNA. Confirmation of the proposed translation mechanism is experimentally tractable and might significantly enhance our understanding of several fundamental biological processes.

scholarly journals microRNA seedless sites attenuate strong-seed-site-mediated target repression

2019 ◽  
Author(s):  
Xujun Wang ◽  
Jingru Tian ◽  
Peng Cui ◽  
Stephen Mastriano ◽  
Dingyao Zhang ◽  
...  
Keyword(s):  
Protein Translation ◽  
Untranslated Regions ◽  
Seed Region ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Attenuation Effect ◽  
Reporter Assays ◽  
Regulate Protein ◽  
Surprising Finding

AbstractMicroRNAs (miRNAs) regulate protein-coding gene expression primarily through cognitive binding sites in the 3’ untranslated regions (3′ UTRs). Seed sites are sequences in messenger RNAs (mRNAs) that form perfect Watson-Crick base-paring with a miRNA’s seed region, which can effectively reduce mRNA abundance and/or repress protein translation. Some seedless sites, which do no form perfect seed-pairing with a miRNA, can also lead to target repression, often with lower efficacy. Here we report the surprising finding that when seedless sites and seed sites are co-present in the same 3’UTR, seedless sites attenuate strong-seed-site-mediated target suppression, independent of 3′ UTR length. This attenuation effect is detectable in >70% of transcriptomic datasets examined, in which specific miRNAs are experimentally increased or decreased. The attenuation effect is confirmed by 3’UTR reporter assays and mediated through base-pairing between miRNA and seedless sites. Furthermore, this seedless-site-based attenuation effect could affect seed sites of the same miRNA or another miRNA, thus partially explaining the variability in target suppression and miRNA-mediated gene upregulation. Our findings reveal an unexpected principle of miRNA-mediated gene regulation, and could impact the understanding of many miRNA-regulated biological processes.

scholarly journals Cell Cycle Control by Nuclear Sequestration ofCDC20andCDH1mRNA in Plant Stem Cells

2017 ◽  
Author(s):  
Weibing Yang ◽  
Raymond Wightman ◽  
Elliot M. Meyerowitz
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization ◽  
Cell Cycle Control ◽  
Protein Translation ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Nuclear Envelope Breakdown ◽  
And Function ◽  
Necessary And Sufficient

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.

scholarly journals Noncanonical Roles of tRNAs: tRNA Fragments and Beyond

2020 ◽  
Vol 54 (1) ◽  
pp. 47-69 ◽  
Author(s):  
Zhangli Su ◽  
Briana Wilson ◽  
Pankaj Kumar ◽  
Anindya Dutta
Keyword(s):  
Sequence Variation ◽  
Protein Translation ◽  
Nutrient Sensing ◽  
Trna Genes ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Regulatory Pathways ◽  
Transfer Rnas ◽  
Rna Molecules

As one of the most abundant and conserved RNA species, transfer RNAs (tRNAs) are well known for their role in reading the codons on messenger RNAs and translating them into proteins. In this review, we discuss the noncanonical functions of tRNAs. These include tRNAs as precursors to novel small RNA molecules derived from tRNAs, also called tRNA-derived fragments, that are abundant across species and have diverse functions in different biological processes, including regulating protein translation, Argonaute-dependent gene silencing, and more. Furthermore, the role of tRNAs in biosynthesis and other regulatory pathways, including nutrient sensing, splicing, transcription, retroelement regulation, immune response, and apoptosis, is reviewed. Genome organization and sequence variation of tRNA genes are also discussed in light of their noncanonical functions. Lastly, we discuss the recent applications of tRNAs in genome editing and microbiome sequencing.

scholarly journals Competing Endogenous RNA: The Key to Posttranscriptional Regulation

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Rituparno Sen ◽  
Suman Ghosal ◽  
Shaoli Das ◽  
Subrata Balti ◽  
Jayprokas Chakrabarti
Keyword(s):  
Posttranscriptional Regulation ◽  
Circular Rnas ◽  
Biological Processes ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Regulatory Circuit ◽  
Transcriptional Regulatory ◽  
Mirna Sponges ◽  
The Impact

Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs) for microRNAs (miRNAs) with shared miRNAs responses elements (MREs) and act as modulator of miRNA by influencing the available level of miRNA. It has recently been discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding RNAs (lncRNAs), and circular RNAs act as miRNA “sponges” by sharing common MRE, inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs are widely implicated in many biological processes. Recent studies have identified ceRNAs associated with a number of diseases including cancer. This brief review focuses on the molecular mechanism of ceRNA as part of the complex post-transcriptional regulatory circuit in cell and the impact of ceRNAs in development and disease.

scholarly journals Diverse CRISPR-Cas complexes require independent translation of small and large subunits from a single gene

2020 ◽  
Author(s):  
Tess M. McBride ◽  
Evan A. Schwartz ◽  
Abhishek Kumar ◽  
David W. Taylor ◽  
Peter C. Fineran ◽  
...  
Keyword(s):  
Single Gene ◽  
Large Subunit ◽  
Small Subunit ◽  
Type I ◽  
Protein Coding ◽  
Functional Complex ◽  
Internal Translation ◽  
Structural Hybrid ◽  
Adaptive Immune Systems ◽  
Independent Translation

AbstractCRISPR-Cas adaptive immune systems provide prokaryotes with defense against viruses by degradation of specific invading nucleic acids. We investigated the previously uncharacterized type I-D interference complex from Synechocystis and revealed it is a genetic and structural hybrid with similarity to both type I and III systems. Surprisingly, formation of the functional complex required internal in-frame translation of small subunits from within the large subunit gene. We further show that internal translation to generate small subunits is widespread across diverse type I-D, I-B and I-C systems, which account for roughly one quarter of CRISPR-Cas systems. Our work reveals the unexpected expansion of protein coding potential from within single cas genes, which has important implications for understanding CRISPR-Cas function and evolution.One Sentence SummaryInternal translation of large subunit transcripts drives small subunit synthesis in diverse type I CRISPR-Cas interference complexes

scholarly journals Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

2016 ◽  
Vol 2 (1) ◽  
pp. 5
Author(s):  
Yu Cuiyun ◽  
Qian Ning ◽  
Zhi-Ping Li ◽  
Wen Huang ◽  
Jia Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Open Reading Frame ◽  
Regulation Mechanism ◽  
Biological Processes ◽  
Biological Functions ◽  
Protein Coding ◽  
Reading Frame ◽  
Rna Molecules ◽  
Non Coding Rnas ◽  
Diagnosis Therapy

<p align="left">Non-coding RNAs (ncRNA) are RNA molecules without protein coding functions owing to the lack of an open reading frame (ORF). Based on the length, ncRNAs can be divided into long and short ncRNAs; short ncRNAs include miRNAs and piRNAs. Hepatocellular carcinoma (HCC) is among the most frequent forms of cancer worldwide and its incidence is increasing rapidly. Studies have found that ncRNAs are likely to play a crucial role in a variety of biological processes including the pathogenesis and progression of HCC. In this review, we summarized the regulation mechanism and biological functions of ncRNAs in HCC with respect to its application in HCC diagnosis, therapy and prognosis.</p>

scholarly journals A congruent phylogenomic signal places eukaryotes within the Archaea

2012 ◽  
Vol 279 (1749) ◽  
pp. 4870-4879 ◽  
Author(s):  
Tom A. Williams ◽  
Peter G. Foster ◽  
Tom M. W. Nye ◽  
Cymon J. Cox ◽  
T. Martin Embley
Keyword(s):  
Ribosomal Rna ◽  
Biological Diversity ◽  
Common Ancestor ◽  
Phylogenetic Analyses ◽  
Large Subunit ◽  
Small Subunit ◽  
Evolutionary Models ◽  
Protein Coding ◽  
Cellular Life ◽  
Phylogenetic Methods

Determining the relationships among the major groups of cellular life is important for understanding the evolution of biological diversity, but is difficult given the enormous time spans involved. In the textbook ‘three domains’ tree based on informational genes, eukaryotes and Archaea share a common ancestor to the exclusion of Bacteria. However, some phylogenetic analyses of the same data have placed eukaryotes within the Archaea, as the nearest relatives of different archaeal lineages. We compared the support for these competing hypotheses using sophisticated phylogenetic methods and an improved sampling of archaeal biodiversity. We also employed both new and existing tests of phylogenetic congruence to explore the level of uncertainty and conflict in the data. Our analyses suggested that much of the observed incongruence is weakly supported or associated with poorly fitting evolutionary models. All of our phylogenetic analyses, whether on small subunit and large subunit ribosomal RNA or concatenated protein-coding genes, recovered a monophyletic group containing eukaryotes and the TACK archaeal superphylum comprising the Thaumarchaeota, Aigarchaeota, Crenarchaeota and Korarchaeota. Hence, while our results provide no support for the iconic three-domain tree of life, they are consistent with an extended eocyte hypothesis whereby vital components of the eukaryotic nuclear lineage originated from within the archaeal radiation.

Depletion and Reconstitution of Active E. Coli Ribosomes

1975 ◽  
Vol 33 ◽  
pp. 640-641
Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins
Keyword(s):  
Protein Biosynthesis ◽  
Large Subunit ◽  
High Resolution Electron Microscopy ◽  
Small Subunit ◽  
Structure And Function ◽  
Biologically Active ◽  
Biological Macromolecules ◽  
E Coli ◽  
Resolution Electron ◽  
And Function

Correlations between structure and function of biological macromolecules have been studied intensively for many years, mostly by indirect methods. High resolution electron microscopy is a unique tool which can provide such information directly by comparing the conformation of biopolymers in their biologically active and inactive state. We have correlated the structure and function of ribosomes, ribonucleoprotein particles which are the site of protein biosynthesis. 70S E. coli ribosomes, used in this experiment, are composed of two subunits - large (50S) and small (30S). The large subunit consists of 34 proteins and two different ribonucleic acid molecules. The small subunit contains 21 proteins and one RNA molecule. All proteins (with the exception of L7 and L12) are present in one copy per ribosome.This study deals with the changes in the fine structure of E. coli ribosomes depleted of proteins L7 and L12. These proteins are unique in many aspects.

Theileria parva ribosomal internal transcribed spacer sequences exhibit extensive polymorphism and mosaic evolution: application to the characterization of parasites from cattle and buffalo

Parasitology ◽  
1999 ◽  
Vol 118 (6) ◽  
pp. 541-551 ◽  
Author(s):  
N. E. COLLINS ◽  
B. A. ALLSOPP
Keyword(s):  
Genetic Recombination ◽  
Large Subunit ◽  
Small Subunit ◽  
Internal Transcribed Spacers ◽  
Rrna Genes ◽  
Gene Pools ◽  
Theileria Parva ◽  
Causative Agents ◽  
Internal Transcribed Spacer Sequences

We sequenced the rRNA genes and internal transcribed spacers (ITS) of several Theileria parva isolates in an attempt to distinguish between the causative agents of East coast fever and Corridor disease. The small subunit (SSU) and large subunit (LSU) rRNA genes from a cloned T. p. lawrencei parasite were sequenced; the former was identical to that of T. p. parva Muguga, and there were minor heterogeneities in the latter. The 5·8S gene sequences of 11 T. parva isolates were identical, but major differences were found in the ITS. Six characterization oligonucleotides were designed to hybridize within the variable ITS1 region; 93·5% of T. p. parva isolates examined were detected by probe TPP1 and 81·8% of T. p. lawrencei isolates were detected by TPL2 and/or TPL3a. There was no absolute distinction between T. p. parva and T. p. lawrencei and the former hybridized with fewer of the probes than did the latter. It therefore seems that a relatively homogenous subpopulation of T. parva has been selected in cattle from a more diverse gene pool in buffalo. The ITSs of both T. p. parva and T. p. lawrencei contained different combinations of identifiable sequence segments, resulting in a mosaic of segments in any one isolate, suggesting that the two populations undergo genetic recombination and that their gene pools are not completely separate.

scholarly journals Domains for protein-protein interactions at the N and C termini of the large subunit of bacteriophage lambda terminase.

Genetics ◽  
1988 ◽  
Vol 119 (3) ◽  
pp. 477-484
Author(s):  
W F Wu ◽  
S Christiansen ◽  
M Feiss
Keyword(s):  
Protein Interactions ◽  
Ternary Complex ◽  
Large Subunit ◽  
Small Subunit ◽  
Functional Domain ◽  
Binary Complex ◽  
Protein Protein Interactions ◽  
Related Phage ◽  
Carboxy Terminal ◽  
Lambda Dna

Abstract The large subunit of phage lambda terminase, gpA, the gene product of the phage A gene, interacts with the small subunit, gpNul, to form functional terminase. Terminase binds to lambda DNA at cosB to form a binary complex. The terminase:DNA complex binds a prohead to form a ternary complex. Ternary complex formation involves an interaction of the prohead with gpA. The amino terminus of gpA contains a functional domain for interaction with gpNul, and the carboxy-terminal 38 amino acids of gpA contain a functional domain for prohead binding. This information about the structure of gpA was obtained through the use of hybrid phages resulting from recombination between lambda and the related phage 21. lambda and 21 encode terminases that are analogous in structural organization and have ca. 60% sequence identity. In spite of these similarities, lambda and 21 terminases differ in specificity for DNA binding, subunit assembly, and prohead binding. A lambda-21 hybrid phage produces a terminase in which one of the subunits is chimeric and had recombinant specificities. In the work reported here; a new hybrid, lambda-21 hybrid 67, is characterized. lambda-21 hybrid 67 is the result of a crossover between lambda and 21 in the large subunit genes, such that the DNA from the left chromosome end is from 21, including cosB phi 21, the 1 gene, and the first 48 codons for the 2 gene. The rest of the hybrid 67 chromosome is lambda DNA, including 593 codons of the A gene. The chimeric gp2/A of hybrid 67 binds gp1 to form functional terminase.(ABSTRACT TRUNCATED AT 250 WORDS)

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