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J Fütterer

Publications and source records attributed to J Fütterer.

At least 19 recordsLinked to original sources

Tissue-specific silencing of a transgene in rice.

In a transgenic rice line, a beta-glucuronidase reporter gene under the control of the rice tungro bacilliform virus promoter became gradually methylated, and gene activity was lost concomitantly. Methylation was observed only in the homozygous offspring and was initially restricted to the promoter region and accompanied by loss of expression in the vascular bundle tissue only. This expression pattern was similar to that of a promoter with a deletion of a vascular bundle expression element. The gene activity could be reestablished by treatment with 5-azacytidine. Methylation per se did not inhibit the binding to the promoter region of protein factors which also bound to the unmethylated sequence. Instead, promoter methylation enabled the alternative binding of a protein with specificity for sequence and methylation. In further generations of homozygous offspring the methylation spread into the transcribed region and gene activity was completely repressed also in nonvascular cells. The results indicate that different stages are involved in DNA methylation-correlated gene inactivation, and that at least one of them may involve the attraction of a sequence and methylation-specific DNA-binding protein.

Badnavirus↗

Shunting is a translation strategy used by plant pararetroviruses (Caulimoviridae).

In eukaryotes standard initiation of translation involved 40S ribosome scanning to bridge the distance from the cap to the initiation codon. Recently deviations from that rule had been described, including "internal initiation", "poly-A dependent translation", and "ribosome shunting". In ribosome shunting, ribosomes start scanning at the cap but large portions of the leader are skipped. Thereby the secondary structure of the shunted region is preserved. Scanning in plant caulimoviruses involve a small open reading frame properly spaced in front of a strong stem structure, and, in order to function, the small open reading frome has to be translated and the peptide released. This arrangement can be mimicked by artificial small open reading frames and stem structures. Shunting with viral and synthetic leaders occurs not only in plant-, but also in mammalian and yeast systems. Thus it responds to an intrinsic property of the eukaryotic translational machinery and probably acts in many cases where coding regions are preceded by complex leaders.

Caulimovirus↗

Simultaneous analysis of the bidirectional African cassava mosaic virus promoter activity using two different luciferase genes.

The expression of geminivirus genes is controlled by bidirectional promoters which are located in the large intergenic region of the circular DNA genomes and specifically regulated by virus encoded proteins. In order to study the simultaneous regulation of both orientations of the DNA A and DNA B promoters of African cassava mosaic virus (ACMV), they were cloned between two different luciferase genes with the firefly luciferase gene in complementary-sense and the Renilla luciferase gene in virion-sense orientation. The regulation of the ACMV promoters by proteins encoded by the complete DNA A, as well as by the individually expressed transactivator (TrAP) or replication-associated (Rep) proteins was assessed in tobacco and cassava protoplasts using dual luciferase assays. In addition, the regulation of the DNA A promoter integrated into tobacco genome was also assessed. The results show that TrAP activates virion-sense expression strongly both in cassava and tobacco protoplasts, but not in transgenic tobacco plants. In contrast to this, DNA A encoded proteins activate virion-sense expression both in protoplasts and in transgenic plants. At the same time they reduce the expression of the complementary-sense Rep gene on DNA A but activate the expression of the complementary-sense movement protein (MPB) gene on DNA B. The degree of MBP activation is higher in cassava than in tobacco protoplasts, indicating that the plant host also influences the promoter strength. Transient transformation experiments using linearized DNA indicate that the different regulation of the ACMV DNA A promoter in protoplasts and transgenic plants could be due to different DNA curvature in free plasmids and in genes integrated in plant genomic DNA.

Geminiviridae↗

Polyadenylation in rice tungro bacilliform virus: cis-acting signals and regulation.

The polyadenylation signal of rice tungro bacilliform virus (RTBV) was characterized by mutational and deletion analysis. The cis-acting signals required to direct polyadenylation conformed to what is known for plant poly(A) signals in general and were very similar to those of the related cauliflower mosaic virus. Processing was directed by a canonical AAUAAA poly(A) signal, an upstream UG-rich region considerably enhanced processing efficiency, and sequences downstream of the cleavage site were not required. When present at the end of a transcription unit, the cis-acting signals for 3'-end processing were highly efficient in both monocot (rice) and dicot (Nicotiana plumbaginifolia) protoplasts. In a promoter-proximal position, as in the viral genome, the signal was also efficiently processed in rice protoplasts, giving rise to an abundant "short-stop" (SS-) RNA. The proportion of SS-RNA was considerably lower in N. plumbaginifolia protoplasts. In infected plants, SS-RNA was hardly detectable, suggesting either that SS-RNA is unstable in infected plants or that read-through of the promoter-proximal poly(A) site is very efficient. SS-RNA is readily detectable in transgenic rice plants (A. Klöti, C. Henrich, S. Bieri, X. He, G. Chen, P. K. Burkhardt, J. Wünn, P. Lucca, T. Hohn, I. Potrylus, and J. Fütterer, 1999. Plant Mol. Biol. 40:249-266), thus the absence of SS-RNA in infected plants can be attributed to poly(A) site bypass in the viral context to ensure production of the full-length pregenomic viral RNA. RTBV poly(A) site suppression thus depends both on context and the expression system; our results suggest that the circular viral minichromosome directs assembly of a transcription-processing complex with specific properties to effect read-through of the promoter-proximal poly(A) signal.

Badnavirus↗

Sequence-specific and methylation-dependent and -independent binding of rice nuclear proteins to a rice tungro bacilliform virus vascular bundle expression element.

Nuclear proteins from rice (Oryza sativa) were identified that bind specifically to a rice tungro bacilliform virus promoter region containing a vascular bundle expression element (VBE). One set of proteins of 29, 33, and 37 kDa, present in shoot and cell suspension extracts but hardly detectable in root extracts, bound to a site containing the sequence AGAAGGACCAGA within the VBE, which also contains two CpG and one CpNpG potential methylation motifs. Binding by these proteins was determined to be cytosine methylation-independent. However, a novel protein present in all analyzed extracts bound specifically to the methylated VBE. A region of at least 49 nucleotides overlapping the VBE and complete cytosine methylation of the three Cp(Np)G motifs was required for efficient binding of this methylated VBE-binding protein (MVBP).

5-Methylcytosine↗

Role of a short open reading frame in ribosome shunt on the cauliflower mosaic virus RNA leader.

The pregenomic 35 S RNA of cauliflower mosaic virus (CaMV) belongs to the growing number of mRNAs known to have a complex leader sequence. The 612-nucleotide leader contains several short open reading frames (sORFs) and forms an extended hairpin structure. Downstream translation of 35 S RNA is nevertheless possible due to the ribosome shunt mechanism, by which ribosomes are directly transferred from a take-off site near the capped 5' end of the leader to a landing site near its 3' end. There they resume scanning and reach the first long open reading frame. We investigated in detail how the multiple sORFs influence ribosome migration either via shunting or linear scanning along the CaMV leader. The sORFs together constituted a major barrier for the linear ribosome migration, whereas the most 5'-proximal sORF, sORF A, in combination with sORFs B and C, played a positive role in translation downstream of the leader by diverting scanning ribosomes to the shunt route. A simplified, shunt-competent leader was constructed with the most part of the hairpin including all the sORFs except sORF A replaced by a scanning-inhibiting structure. In this leader as well as in the wild type leader, proper translation and termination of sORF A was required for efficient shunt and also for the level of shunt enhancement by a CaMV-encoded translation transactivator. sORF A could be replaced by heterologous sORFs, but a one-codon (start/stop) sORF was not functional. The results implicate that in CaMV, shunt-mediated translation requires reinitiation. The efficiency of the shunt process is influenced by translational properties of the sORF.

5' Untranslated Regions↗

Transcriptional activation of the rice tungro bacilliform virus gene is critically dependent on an activator element located immediately upstream of the TATA box.

To investigate the transcriptional mechanisms of rice tungro bacilliform virus, we have systematically analyzed an activator element located immediately upstream of the TATA box in the rice tungro bacilliform virus promoter and its cognate trans-acting factors. Using electrophoretic mobility shift assays, we showed that rice nuclear proteins bind to the activator element, forming multiple specific DNA-protein complexes via protein-protein interactions. Copper-phenanthroline footprinting and DNA methylation interference analysis indicated that multiple DNA-protein complexes share a common binding site located between positions -60 to -39, and the proteins contact the activator element in the major groove. DNA UV cross-linking assays further showed that two nuclear proteins (36 and 33 kDa), found in rice cell suspension and shoot nuclear extracts, and one (27 kDa), present in root nuclear extracts, bind to this activator element. In protoplasts derived from a rice (Oryza sativa) suspension culture, the activator element is a prerequisite for promoter activity and its function is critically dependent on its position relative to the TATA box. Thus, transcriptional activation may function via interactions with the basal transcriptional machinery, and we propose that this activation is mediated by protein-protein interactions in a position-dependent mechanism.

Badnavirus↗

Upstream and downstream sequence elements determine the specificity of the rice tungro bacilliform virus promoter and influence RNA production after transcription initiation.

The contribution of sequences upstream and downstream of the transcription start site to the strength and specificity of the promoter of rice tungro bacilliform virus was analysed in transgenic rice plants. The promoter is strongly stimulated by downstream sequences which include an intron and is active in all vascular and epidermal cells. Expression in the vascular tissue requires a promoter element located between -100 and -164 to which protein(s) from rice nuclear extracts bind. Elimination of this region leads to specificity for the epidermis. Due to the presence of a polyadenylation signal in the intron, short-stop RNA is produced from the promoter in addition to full-length primary transcript and its spliced derivatives. The ratio between short-stop RNA and full-length or spliced RNA is determined by upstream promoter sequences, suggesting the assembly of RNA polymerase complexes with different processivity on this promoter.

Badnavirus↗

Ribosome shunting in cauliflower mosaic virus. Identification of an essential and sufficient structural element.

A wheat germ cell-free system was used to study details of ribosome shunting promoted by the cauliflower mosaic virus 35 S RNA leader. By testing a dicistronic construct with the leader placed between two coding regions, we confirmed that the 35 S RNA leader does not include an internal ribosome entry site of the type observed with picornavirus RNAs. A reporter gene fused to the leader was shown to be expressed by ribosomes that had followed the bypass route (shunted) and, with lower efficiency, by ribosomes that had scanned through the whole region. Stem section 1, the most stable of the three stem sections of the leader, was shown to be an important structural element for shunting. Mutations that abolished formation of this stem section drastically reduced reporter gene expression, whereas complementary mutations that restored stem section 1 also restored shunting. A micro-leader capable of shunting consisting of stem section 1 and flanking sequences could be defined. A small open reading frame preceding stem section 1 enhances shunting.

Base Composition↗

Forced evolution reveals the importance of short open reading frame A and secondary structure in the cauliflower mosaic virus 35S RNA leader.

Cauliflower mosaic virus pregenomic 35S RNA begins with a long leader sequence containing an extensive secondary structure and up to nine short open reading frames (sORFs), 2 to 35 codons in length. To test whether any of these sORFs are required for virus viability, their start codons were mutated either individually or in various combinations. The resulting viral mutants were tested for infectivity on mechanically inoculated turnip plants. Viable mutants were passaged several times, and the stability of the introduced mutations was analyzed by PCR amplification and sequencing. Mutations at the 5'-proximal sORF A and in the center of the leader resulted in delayed symptom development and in the appearance of revertants. In the central leader region, the predicted secondary structure, rather than the sORF organization, was restored, while true reversions or second-site substitutions in response to mutations of sORF A restored this sORF. Involvement of sORF A and secondary structure of the leader in the virus replication cycle, and especially in translation of the 35S RNA via ribosome shunting, is discussed.

Base Sequence↗

Rice tungro bacilliform virus open reading frames II and III are translated from polycistronic pregenomic RNA by leaky scanning.

Posttranscriptional components of the gene expression mechanism of rice tungro bacilliform virus (RTBV) were studied in transiently transfected protoplasts. RTBV translates several open reading frames from a polycistronic mRNA by leaky scanning. This mechanism is supported by the particular sequence features of the corresponding genome region and does not require a virus-encoded transactivator.

Badnavirus↗

Translation in plants--rules and exceptions.

Translation processes in plants are very similar to those in other eukaryotic organisms and can in general be explained with the scanning model. Particularly among plant viruses, unconventional mRNAs are frequent, which use modulated translation processes for their expression: leaky scanning, translational stop codon readthrough or frameshifting, and transactivation by virus-encoded proteins are used to translate polycistronic mRNAs; leader and trailer sequences confer (cap-independent) efficient ribosome binding, usually in an end-dependent mechanism, but true internal ribosome entry may occur as well; in a ribosome shunt, sequences within an RNA can be bypassed by scanning ribosomes. Translation in plant cells is regulated under conditions of stress and during development, but the underlying molecular mechanisms have not yet been determined. Only a small number of plant mRNAs, whose structure suggests that they might require some unusual translation mechanisms, have been described.

Plants↗

Efficient transcription from the rice tungro bacilliform virus promoter requires elements downstream of the transcription start site.

Elements downstream of the transcription start site enhance the activity of the rice tungro bacilliform virus (RTBV) promoter in protoplasts derived from cultured rice cells. This enhancer region was located to the first 90 nucleotides of the RTBV leader sequence. Within this region, at least two components which act together to enhance expression from the RTBV promoter could be identified. One is a position- and orientation-independent DNA element within a CT-rich region, and the other is a position-dependent element. Either element was found to be capable of acting independently on a heterologous promoter. The enhancer activity of the DNA element correlates with specific binding of nuclear proteins. Nuclear proteins also recognize an RNA transcript covering the first 90 nucleotides of the RTBV leader.

Badnavirus↗

Position-dependent ATT initiation during plant pararetrovirus rice tungro bacilliform virus translation.

The expression of the rice tungro bacilliform virus open reading frame I was studied in transiently transfected protoplasts. Expression occurs despite the presence of a long leader sequence and the absence of a proper ATG initiation codon. Translation is initiated at an ATT codon. The efficiency of initiation in rice protoplasts depends strongly on the mechanism by which ribosomes reach this codon. From the effects of scanning-inhibiting structures inserted into different leader regions, it can be deduced that this mechanism is related to the ribosome shunt described for cauliflower mosaic virus 35S RNA. The process delivers initiation-competent ribosomes to the region downstream of the leader and is so precise that only the second of two potential start codons only 12 nucleotides apart is recognized. The ATT codon that is used when it is present downstream of the leader is hardly recognized as a start codon by ribosomes that reach it by scanning.

Base Sequence↗

"Horizontal" gene transfer from a transgenic potato line to a bacterial pathogen (Erwinia chrysanthemi) occurs--if at all--at an extremely low frequency.

The frequency of possible "horizontal" gene transfer between a plant and a tightly associated bacterial pathogen was studied in a model system consisting of transgenic Solanum tuberosum, containing a beta-lactamase gene linked to a pBR322 origin of replication, and Erwinia chrysanthemi. This experimental system offers optimal conditions for the detection of possible horizontal gene transfer events, even when they occur at very low frequency. Horizontal gene transfer was not detected under conditions mimicking a "natural" infection. The gradual, stepwise alteration of artificial, positive control conditions to idealized natural conditions, however, allowed the characterization of factors that affected gene transfer, and revealed a gradual decrease of the gene transfer frequency from 6.3 x 10(-2) under optimal control conditions to a calculated 2.0 x 10(-17) under idealized natural conditions. These data, in combination with other published studies, argue that horizontal gene transfer is so rare as to be essentially irrelevant to any realistic assessment of the risk involved in release experiments involving transgenic plants.

Ampicillin↗

Splicing in a plant pararetrovirus.

Analysis of expression in rice cells of plasmids in which an ATG-less chloramphenicol acetyl transferase ORF was placed in frame with the coding sequence of the pararetrovirus rice tungro bacilliform virus (RTBV) ORF IV, and which contained much of the upstream full-length transcript sequence of RTBV, gave evidence to suggest that a splicing event occurred. Reverse transcription/PCR of RNA from transfected protoplasts and from RTBV-infected plants yielded a product which confirmed that the 5' end of ORF IV was spliced in frame to a short ORF (sORF) in the RTBV leader sequence removing an intron of about 6.3 kb. Most of the translation is initiated at the ATG codon in the sORF with only about 10% at the ORF IV ATG codon. The efficiency of splicing appears to be inversely related to the length of the intron. The finding of splicing in a pararetrovirus blurs the differences between them and retroviruses but is in accord with the hypothesis that retroelements acquire genes and sequences which adapt them to specific niches.

Base Sequence↗

Rice tungro bacilliform virus: transcription and translation in protoplasts.

Protoplasts from cell suspension cultures of Oryza sativa (monocot) and Orychophragmus violaceus (dicot) support transcription from the rice tungro bacilliform virus (RTBV) promoter and translation of the resulting mRNA despite the presence of a long leader sequence with strong secondary structure and 12 short open reading frames. Transcriptional elements located both upstream and downstream of the transcription initiation site are defined by deletion analysis and the functional TATA motif is determined. Expression of an open reading frame downstream of the entire leader is more efficient than that downstream of truncated derivatives. For optimal expression sequences in the 5' and 3' parts of the leader are required.

Base Sequence↗