scholarly journals Characterizing Transcriptional Regulatory Sequences in Coronaviruses and Their Role in Recombination

2020 ◽  
Author(s):  
Yiyan Yang ◽  
Wei Yan ◽  
A Brantley Hall ◽  
Xiaofang Jiang
Keyword(s):  
Secondary Structure ◽  
Rna Viruses ◽  
Leader Sequence ◽  
Template Switching ◽  
Regulatory Sequences ◽  
Core Sequence ◽  
Recombination Hotspots ◽  
Transcriptional Regulatory ◽  
Recombination Breakpoints

Abstract Novel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3,509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently colocated with TRS-B sites than expected.

scholarly journals Characterizing transcriptional regulatory sequences in coronaviruses and their role in recombination

2020 ◽  
Author(s):  
Yiyan Yang ◽  
Wei Yan ◽  
A. Brantley Hall ◽  
Xiaofang Jiang
Keyword(s):  
Secondary Structure ◽  
Rna Viruses ◽  
Leader Sequence ◽  
Template Switching ◽  
Regulatory Sequences ◽  
Core Sequence ◽  
Recombination Hotspots ◽  
Transcriptional Regulatory ◽  
Recombination Breakpoints

ABSTRACTNovel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently co-located with TRS-B sites than expected.

scholarly journals Conserved recombination patterns across coronavirus subgenera

2021 ◽  
Author(s):  
Arne de Klerk ◽  
Phillip Ivan Swanepoel ◽  
Rentia Francis Lourens ◽  
Mpumelelo Zondo ◽  
Isaac Abodunran ◽  
...  
Keyword(s):  
Sequence Data ◽  
Hot Spot ◽  
Recombination Breakpoint ◽  
Whole Genome Sequence ◽  
Template Switching ◽  
Regulatory Sequences ◽  
Spike Gene ◽  
Sequence Features ◽  
Transcriptional Regulatory ◽  
Recombination Breakpoints

Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination breakpoints at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination breakpoints across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination breakpoint hot-spot locations. We find that while the locations of recombination breakpoints are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination breakpoints most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination breakpoint distributions in coronavirus genomes sampled from nature.

scholarly journals Evidence of Recombination in the Norovirus Capsid Gene

2005 ◽  
Vol 79 (8) ◽  
pp. 4977-4990 ◽  
Author(s):  
Jacques Rohayem ◽  
Julia Münch ◽  
Axel Rethwilm
Keyword(s):  
Secondary Structure ◽  
Rna Secondary Structure ◽  
Rna Viruses ◽  
Capsid Gene ◽  
Clinical Samples ◽  
Genomic Variability ◽  
Sequence Composition ◽  
Genetic Clusters ◽  
Complete Capsid ◽  
Recombination Breakpoints

ABSTRACT Noroviruses are single-stranded RNA viruses with high genomic variability. They have emerged in the last decade as a major cause of acute gastroenteritis. It remains so far unclear whether norovirus evolution is driven by sequence mutation and/or recombination. In this study, we have assessed the occurrence of recombination in the norovirus capsid gene. For this purpose, 69 complete capsid sequences of norovirus strains accessible in GenBank as well as 25 complete capsid sequences generated from norovirus-positive clinical samples were examined. Unreported recombination was detected in about 8% of norovirus strains belonging to genetic clusters I/1 (n = 1), II/1 (n = 1), II/3 (n = 1), II/4 (n = 3), and II/5 (n = 1). Recombination breakpoints were mainly located at the interface of the putative P1-1 and P2 domains of the capsid protein and/or within the P2 domain. The recombination region displayed features such as length, sequence composition (upstream and downstream GC- and AU-rich sequences, respectively), and predicted RNA secondary structure that are characteristic of homologous recombination activators. Our results suggest that recombination in the norovirus capsid gene may naturally occur, involving capsid domains presumably exposed to immunological pressure.

scholarly journals Lack of Association between Human Switch Recombination Breakpoints and the Secondary Structure of Targeted DNA Regions

2004 ◽  
Vol 172 (5) ◽  
pp. 2727.1-2727 ◽  
Author(s):  
Qiang Pan-Hammarström ◽  
Yaofeng Zhao ◽  
Lennart Hammarström
Keyword(s):  
Secondary Structure ◽  
Recombination Breakpoints

A variant octamer motif in a Xenopus H2B histone gene promoter is not required for transcription in frog oocytes

1991 ◽  
Vol 11 (2) ◽  
pp. 641-654
Author(s):  
C Hinkley ◽  
M Perry
Keyword(s):  
Cell Cycle ◽  
Transcription Initiation ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Histone Gene ◽  
Site Directed Mutagenesis ◽  
Regulatory Sequences ◽  
Chromosomal Dna ◽  
Transcriptional Regulatory ◽  
Octamer Motif

Xenopus oocytes, arrested in G2 before the first meiotic division, accumulate histone mRNA and protein in the absence of chromosomal DNA replication and therefore represent an attractive biological system in which to examine histone gene expression uncoupled from the cell cycle. Previous studies have shown that sequences necessary for maximal levels of transcription in oocytes are present within 200 bp at the 5' end of the transcription initiation site for genes encoding each of the five major Xenopus histone classes. We have defined by site-directed mutagenesis individual regulatory sequences and characterized DNA-binding proteins required for histone H2B gene transcription in injected oocytes. The Xenopus H2B gene has a relatively simple promoter containing several transcriptional regulatory elements, including TFIID, CBP, and ATF/CREB binding sites, required for maximal transcription. A sequence (CTTTACAT) in the H2B promoter resembling the conserved octamer motif (ATTTGCAT), the target for cell-cycle regulation of a human H2B gene, is not required for transcription in oocytes. Nonetheless, substitution of a consensus octamer motif for the variant octamer element activates H2B transcription. Oocyte factors, presumably including the ubiquitous Oct-1 factor, specifically bind to the consensus octamer motif but not to the variant sequence. Our results demonstrate that a transcriptional regulatory element involved in lymphoid-specific expression of immunoglobulin genes and in S-phase-specific activation of mammalian H2B histone genes can activate transcription in nondividing amphibian oocytes.

scholarly journals Identification of a functional NF-kappa B binding site in the murine T cell receptor beta 2 locus.

1989 ◽  
Vol 170 (5) ◽  
pp. 1737-1743 ◽  
Author(s):  
C Jamieson ◽  
F Mauxion ◽  
R Sen
Keyword(s):  
T Cell ◽  
Phorbol Esters ◽  
Cell Receptor ◽  
Regulatory Sequences ◽  
Nf Kappa B ◽  
Cellular Activation ◽  
Transcriptional Regulatory ◽  
Hypersensitive Sites ◽  
T Cell Receptor Beta ◽  
Beta 2

We have identified a sequence in the TCR beta 2 locus that is homologous to the kappa B site in the Ig kappa light chain enhancer. This element, TCR beta-B, is located in the vicinity of previously identified T cell-specific DNase1 hypersensitive sites. Transfection analysis shows that a 60-bp fragment encompassing this site is preferentially active in T cells stimulated with phorbol esters or the HTLV-1 tax gene product compared with a B cell line that constitutively expresses NF-kappa B. Our results provide the first evidence for transcriptional regulatory sequences residing within the J beta 2-C beta 2 intron and suggest the possible involvement of these sequences in modulation of TCR beta gene expression upon cellular activation.

P-element-mediated enhancer detection applied to the study of oogenesis in Drosophila

Development ◽  
1989 ◽  
Vol 107 (2) ◽  
pp. 189-200 ◽  
Author(s):  
U. Grossniklaus ◽  
H.J. Bellen ◽  
C. Wilson ◽  
W.J. Gehring
Keyword(s):  
Germ Line ◽  
Expression Patterns ◽  
Cell Types ◽  
Regulatory Elements ◽  
P Element ◽  
Regulatory Sequences ◽  
Transcriptional Regulatory ◽  
Morphological Criteria ◽  
Enhancer Detection ◽  
New Strategies

We have stained the ovaries of nearly 600 different Drosophila strains carrying single copies of a P-element enhancer detector. This transposon detects neighbouring genomic transcriptional regulatory sequences by means of a beta-galactosidase reporter gene. Numerous strains are stained in specific cells and at specific stages of oogenesis and provide useful ovarian markers for cell types that in some cases have not previously been recognized by morphological criteria. Since recent data have suggested that a substantial number of the regulatory elements detected by enhancer detection control neighbouring genes, we discuss the implications of our results concerning ovarian gene expression patterns in Drosophila. We have also identified a small number of insertion-linked recessive mutants that are sterile or lead to ovarian defects. We observe a strong correlation with specific germ line staining patterns in these strains, suggesting that certain patterns are more likely to be associated with female sterile genes than others. On the basis of our results, we suggest new strategies, which are not primarily based on the generation of mutants, to screen for and isolated female sterile genes.

A Drosophila GATA family member that binds to Adh regulatory sequences is expressed in the developing fat body

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 623-633 ◽  
Author(s):  
T. Abel ◽  
A.M. Michelson ◽  
T. Maniatis
Keyword(s):  
Fat Body ◽  
Regulatory Elements ◽  
Drosophila Embryo ◽  
Cdna Clones ◽  
Regulatory Sequences ◽  
Mammalian Development ◽  
Sequence Element ◽  
Gata Factors ◽  
Transcriptional Regulatory ◽  
Gata Family

We have identified a Drosophila transcription factor that binds a sequence element found in the larval promoters of all known alcohol dehydrogenase (Adh) genes. DNA sequence analysis of cDNA clones encoding this protein, box A-binding factor (ABF), reveals that it is a member of the GATA family of transcriptional regulatory factors. ABF-binding sites within the D. mulleri and D. melanogaster larval Adh promoters function as positive regulatory elements and in cotransfection experiments, ABF functions as a transcriptional activator. In further support of a role for ABF in the regulation of Adh expression, ABF mRNA is expressed in the embryonic fat body, a tissue that contains high levels of Adh mRNA. Our studies demonstrate that the fat body develops from segmentally repeated clusters of mesodermal cells, which later expand and coalesce to form the mature fat body. These observations establish ABF as the earliest known fat body precursor marker in the Drosophila embryo. Together with the established role of GATA factors during mammalian development, these results suggest that ABF may play a key role in the organogenesis of the fat body.

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