bicoid mRNA localization signal: phylogenetic conservation of function and RNA secondary structure

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 161-171 ◽  
Author(s):  
P.M. MacDonald
Keyword(s):  
Comparative Analysis ◽  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Rational Design ◽  
Mrna Localization ◽  
Anterior Pole ◽  
Noncoding Regions ◽  
Cis Acting ◽  
Phylogenetic Conservation ◽  
Localization Signal

Transcripts of the bicoid (bcd) gene are localized to the anterior pole of the Drosophila oocyte, thereby allowing formation in the embryo of an anteroposterior gradient of the bcd protein morphogen. We previously showed that a 630 nucleotide portion of the 3′ noncoding region of the bcd mRNA is necessary for this localization, and is sufficient to confer anterior localization on a heterologous transcript. Here I have used a comparative analysis to begin to more precisely define the cis-acting mRNA localization signal. The bcd genes from six additional Drosophila species were cloned, and DNA of the 3′ noncoding regions sequenced. Three of these regions were tested interspecifically for mRNA localization in D. melanogaster and each functioned correctly; these regions must therefore contain the cis-acting signal. The primary sequences, which are up to 50% divergent from the D. melanogaster gene, show patchy homology throughout most of the region. Interestingly, all seven species can potentially form a large stereotypic secondary structure. This structure is a likely candidate for the localization signal and can be used for the rational design of mutations to test that possibility.

RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1233-1243 ◽  
Author(s):  
P.M. Macdonald ◽  
K. Kerr ◽  
J.L. Smith ◽  
A. Leask
Keyword(s):  
Untranslated Region ◽  
Regulatory Element ◽  
Essential Element ◽  
Mrna Localization ◽  
Morphogen Gradient ◽  
Anterior Pole ◽  
Functional Elements ◽  
Cis Acting ◽  
Localization Signal ◽  
Drosophila Embryos

Deployment of the bicoid morphogen gradient in early Drosophila embryos requires the prelocalization of bicoid mRNA to the anterior pole of the egg. This anterior localization is mediated by a cis-acting localization signal contained within the 3′ untranslated region of the bicoid mRNA. Here we use a series of bicoid transgenes carrying small deletions in the 3′ untranslated region to survey for functional elements that constitute the localization signal. We identify and characterize one essential element, BLE1, which specifically directs the early steps of localization. In addition, we find that many deletions within the bicoid mRNA 3′ untranslated region impair but do not prevent localization. One such deletion specifically interferes with a later step in localization. Thus the bicoid mRNA localization signal appears to consist of multiple different elements, each responsible for different steps in the localization process.

Components acting in localization of bicoid mRNA are conserved among Drosophila species.

Genetics ◽  
1994 ◽  
Vol 137 (2) ◽  
pp. 521-530 ◽  
Author(s):  
S K Luk ◽  
M Kilpatrick ◽  
K Kerr ◽  
P M Macdonald
Keyword(s):  
Mrna Localization ◽  
Drosophila Virilis ◽  
Drosophila Species ◽  
Drosophila Pseudoobscura ◽  
Anterior Pole ◽  
Early Step ◽  
Cis Acting ◽  
Body Patterning ◽  
Localization Signal ◽  
Evolutionary Comparisons

Abstract Substantial insights into basic strategies for embryonic body patterning have been obtained from genetic analyses of Drosophila melanogaster. This knowledge has been used in evolutionary comparisons to ask if genes and functions are conserved. To begin to ask how highly conserved are the mechanisms of mRNA localization, a process crucial to Drosophila body patterning, we have focused on the localization of bcd mRNA to the anterior pole of the embryo. Here we consider two components involved in that process: the exuperantia (exu) gene, required for an early step in localization; and the cis-acting signal that directs bcd mRNA localization. First, we use the cloned D. melanogaster exu gene to identify the exu genes from Drosophila virilis and Drosophila pseudoobscura and to isolate them for comparisons at the structural and functional levels. Surprisingly, D. pseudoobscura has two closely related exu genes, while D. melanogaster and D. virilis have only one each. When expressed in D. melanogaster ovaries, the D. virilis exu gene and one of the D. pseudoobscura exu genes can substitute for the endogenous exu gene in supporting localization of bcd mRNA, demonstrating that function is conserved. Second, we reevaluate the ability of the D. pseudoobscura bcd mRNA localization signal to function in D. melanogaster. In contrast to a previous report, we find that function is retained. Thus, among these Drosophila species there is substantial conservation of components acting in mRNA localization, and presumably the mechanisms underlying this process.

scholarly journals Novel sequence variations in LAMA2 and SGCG genes modulating cis-acting regulatory elements and RNA secondary structure

2010 ◽  
Vol 33 (1) ◽  
pp. 190-197 ◽  
Author(s):  
Olfa Siala ◽  
Ikhlass Hadj Salem ◽  
Abdelaziz Tlili ◽  
Imen Ammar ◽  
Hanen Belguith ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Regulatory Elements ◽  
Cis Acting ◽  
Sequence Variations

scholarly journals 3′UTR SL-IV and DB1 Regions Contribute to Japanese Encephalitis Virus Replication and Pathogenicity

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinchao Xing ◽  
Youyue Zhang ◽  
Ziying Lin ◽  
Lele Liu ◽  
Qiang Xu ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Rna Secondary Structure ◽  
Rational Design ◽  
Case Fatality ◽  
Encephalitis Virus ◽  
Reverse Genetic System ◽  
Emerging Pathogens

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV is maintained in an enzootic cycle and causes reproductive failure in pigs. Notably, the shift in JEV genotypes is not fully protected by existing vaccines, so the development of a candidate vaccine is urgently needed. In this study, we compared pathogenicity between Japanese encephalitis virus SA14 and BJB (isolated from humans in the 1970s) strains. We found that the BJB strain was attenuated in mice and that there was no case fatality rate. The growth rate of BJB was higher than SA14 virus in BHK-21 cells. Based on the sequence alignment of the viral genome between the SA14 and BJB virus strains, some mutations at sites 248, 254, 258, and 307 were observed in the 3′ untranslated region (3′UTR). The 3′UTR of JEV plays a very important role in the viral life cycle. Furthermore, using a reverse genetic system, we conducted and rescued the parental JEV strain SA14 (T248, A254, and A258) and the mutant virus rSA14-3′UTRmut (T248C, A254G, A258G, and 307G). Through an analysis of the RNA secondary structure model of the 3′UTR, we discovered that the mutations of T248C, A254G, and A258G reduced the apiculus ring and increased the lateral ring significantly in the stem-loop structures IV (SL-IV) structure region of 3′UTR. Moreover, the insertion of 307G added a ring to the dumbbell structure 1 (DB1) structure region. Strikingly, these RNA secondary structure changes in 3′UTR of rSA14-3′UTRmut increased viral negative chain RNA production and enhanced the replication ability of the virus in BHK-21 cells. However, in vivo mouse experiments illustrated that the rSA14-3′UTRmut virus significantly decreased the neurovirulence of JEV. These results affirmed that the JEV SL-IV and DB1 regions play an important role in viral proliferation and pathogenicity. Taken together, we complement the study of RNA element function in the 3′UTR region of JEV by providing a new target for the rational design of live attenuated candidate vaccines and the increase of virus production.

scholarly journals RNA folding in Drosophila shows a distance effect for compensatory fitness interactions.

Genetics ◽  
1993 ◽  
Vol 135 (1) ◽  
pp. 97-103
Author(s):  
W Stephan ◽  
D A Kirby
Keyword(s):  
Linkage Disequilibrium ◽  
Comparative Analysis ◽  
Secondary Structure ◽  
Messenger Rna ◽  
Rna Secondary Structure ◽  
Rna Folding ◽  
Distance Effect ◽  
Physical Distance ◽  
Random Genetic Drift ◽  
Mutation Pressure

Abstract Phylogenetic-comparative analysis was used to construct a secondary structure of Adh precursor messenger RNA (pre-mRNA) in Drosophila. The analysis revealed that the rate of coevolution of base-pairing residues decreases with their physical distance. This result is in qualitative agreement with a model of compensatory fitness interactions which assumes that mutations are individually deleterious but become harmless (neutral) in appropriate combinations. This model predicts that coupled mutations can become fixed in a population under mutation pressure and random genetic drift, when the mutations are closely linked. However, the rate of joint fixation drops as distance between sites increases and recombination breaks up favorable combinations. RNA secondary structure was also used to interpret patterns of linkage disequilibrium at Adh.

scholarly journals Universal RNA Secondary Structure Insight Into Mosquito-Borne Flavivirus (MBFV) cis-Acting RNA Biology

2020 ◽  
Vol 11 ◽  
Author(s):  
Miao Zeng ◽  
Yanping Duan ◽  
Wei Zhang ◽  
Mingshu Wang ◽  
Renyong Jia ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Cis Acting ◽  
Rna Biology ◽  
Insight Into

scholarly journals Redesigning the Eterna100 for the Vienna 2 folding engine

2021 ◽  
Author(s):  
Rohan V. Koodli ◽  
Boris Rudolfs ◽  
Hannah K. Wayment-Steele ◽  
Rhiju Das ◽  
Keyword(s):  
Neural Network ◽  
Free Energy ◽  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Online Community ◽  
Rational Design ◽  
Structural Features ◽  
Structure Design ◽  
Design Algorithms ◽  
Rna Design

AbstractThe rational design of RNA is becoming important for rapidly developing technologies in medicine and biochemistry. Recent work has led to the development of several RNA secondary structure design algorithms and corresponding benchmarks to evaluate their performance. However, the performance of these algorithms is linked to the nature of the underlying algorithms for predicting secondary structure from sequences. Here, we show that an online community of RNA design experts is capable of modifying an existing RNA secondary structure design benchmark (Eterna100) with minimal alterations to address changes in the folding engine used (Vienna 1.8 updated to Vienna 2.4). We tested this new Eterna100-V2 benchmark with five RNA design algorithms, and found that neural network-based methods exhibited reduced performance in the folding engine they were evaluated on in their respective papers. We investigated this discrepancy, and determined that structural features, previously classified as difficult, may be dependent on parameters inherent to the RNA energy function itself. These findings suggest that for optimal performance, future algorithms should focus on finding strategies capable of solving RNA secondary structure design benchmarks independently of the free energy benchmark used. Eterna100-V1 and Eterna100-V2 benchmarks and example solutions are freely available at https://github.com/eternagame/eterna100-benchmarking.

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