Limits...
In silico structural and functional characterization of the RSUME splice variants.

Gerez J, Fuertes M, Tedesco L, Silberstein S, Sevlever G, Paez-Pereda M, Holsboer F, Turjanski AG, Arzt E - PLoS ONE (2013)

Bottom Line: Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain.We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME.The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET, Buenos Aires, Argentina.

ABSTRACT
RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-κB signaling pathway is inhibited and the HIF-1 pathway is increased more efficiently by the longest RSUME, by means of a greater physical interaction of RSUME267 with the target proteins. In addition, the mRNA and protein levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-κB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.

Show MeSH

Related in: MedlinePlus

The human RSUME splice variants.Schematic illustration of the RSUME pre-mRNA (above) and the four human RSUME mRNA transcripts splice variants documented to the date. The variant 1 (NM_015485) encodes the longest isoform of RSUME containing 267 aminoacids (RSUME267); the variant 2 (NM_ 001128142) encodes the shortest isoform of RSUME containing 195 aminoacids (RSUME195); the variant 3 (NM-001199682) encodes a 200 aminoacids RSUME (RSUME200); and the variant 4 (NR_037643) is a non-coding RNA because it presents a premature stop codon in the exon 2 that goes to degradation via NMD. Boxes, exons with the exon number inside; filled black lines, introns; gray lines, splicing events (filled, splice event that originates the variant 1; dashed, variant 2; dotted, variant 3; streak and point, variant 4); +1, transcription start site; AUG, translation start site; UAA, UGA and UAG, translation stop sites. This information was obtained from published sequences in the University of California, Santa Cruz, genome browser (http://genome.ucsc.edu/).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585135&req=5

pone-0057795-g001: The human RSUME splice variants.Schematic illustration of the RSUME pre-mRNA (above) and the four human RSUME mRNA transcripts splice variants documented to the date. The variant 1 (NM_015485) encodes the longest isoform of RSUME containing 267 aminoacids (RSUME267); the variant 2 (NM_ 001128142) encodes the shortest isoform of RSUME containing 195 aminoacids (RSUME195); the variant 3 (NM-001199682) encodes a 200 aminoacids RSUME (RSUME200); and the variant 4 (NR_037643) is a non-coding RNA because it presents a premature stop codon in the exon 2 that goes to degradation via NMD. Boxes, exons with the exon number inside; filled black lines, introns; gray lines, splicing events (filled, splice event that originates the variant 1; dashed, variant 2; dotted, variant 3; streak and point, variant 4); +1, transcription start site; AUG, translation start site; UAA, UGA and UAG, translation stop sites. This information was obtained from published sequences in the University of California, Santa Cruz, genome browser (http://genome.ucsc.edu/).

Mentions: Four coding human RSUME mRNA transcripts have been described to date (based on RefSeq database), named RWDD3 (from RWD-domain containing 3) transcript variant 1, 2 and 3, and non-coding RNA. While the variant 1 (NM_015485) has 4 out of 5 exons and encodes the longest RSUME isoform, the transcript variant 2 (NM_001128142) has the longest exon 3, lacks exons 2 and 4, and encodes the shortest isoform. The variant 3 (NM_001199682) does not include exon 2 and has the shortest exon 3. The RSUME mRNA transcripts variants 1, 2 and 3 codify for RSUME isoforms of 267, 195 and 200 aminoacids, named RSUME267, RSUME195 and RSUME200, respectively (Fig. 1). The non-coding RNA (NR_037643) contains all the exons but presents a premature stop codon in the exon 2 that leads it to degradation via NMD. Because of this, such variant does not encode any protein.


In silico structural and functional characterization of the RSUME splice variants.

Gerez J, Fuertes M, Tedesco L, Silberstein S, Sevlever G, Paez-Pereda M, Holsboer F, Turjanski AG, Arzt E - PLoS ONE (2013)

The human RSUME splice variants.Schematic illustration of the RSUME pre-mRNA (above) and the four human RSUME mRNA transcripts splice variants documented to the date. The variant 1 (NM_015485) encodes the longest isoform of RSUME containing 267 aminoacids (RSUME267); the variant 2 (NM_ 001128142) encodes the shortest isoform of RSUME containing 195 aminoacids (RSUME195); the variant 3 (NM-001199682) encodes a 200 aminoacids RSUME (RSUME200); and the variant 4 (NR_037643) is a non-coding RNA because it presents a premature stop codon in the exon 2 that goes to degradation via NMD. Boxes, exons with the exon number inside; filled black lines, introns; gray lines, splicing events (filled, splice event that originates the variant 1; dashed, variant 2; dotted, variant 3; streak and point, variant 4); +1, transcription start site; AUG, translation start site; UAA, UGA and UAG, translation stop sites. This information was obtained from published sequences in the University of California, Santa Cruz, genome browser (http://genome.ucsc.edu/).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585135&req=5

pone-0057795-g001: The human RSUME splice variants.Schematic illustration of the RSUME pre-mRNA (above) and the four human RSUME mRNA transcripts splice variants documented to the date. The variant 1 (NM_015485) encodes the longest isoform of RSUME containing 267 aminoacids (RSUME267); the variant 2 (NM_ 001128142) encodes the shortest isoform of RSUME containing 195 aminoacids (RSUME195); the variant 3 (NM-001199682) encodes a 200 aminoacids RSUME (RSUME200); and the variant 4 (NR_037643) is a non-coding RNA because it presents a premature stop codon in the exon 2 that goes to degradation via NMD. Boxes, exons with the exon number inside; filled black lines, introns; gray lines, splicing events (filled, splice event that originates the variant 1; dashed, variant 2; dotted, variant 3; streak and point, variant 4); +1, transcription start site; AUG, translation start site; UAA, UGA and UAG, translation stop sites. This information was obtained from published sequences in the University of California, Santa Cruz, genome browser (http://genome.ucsc.edu/).
Mentions: Four coding human RSUME mRNA transcripts have been described to date (based on RefSeq database), named RWDD3 (from RWD-domain containing 3) transcript variant 1, 2 and 3, and non-coding RNA. While the variant 1 (NM_015485) has 4 out of 5 exons and encodes the longest RSUME isoform, the transcript variant 2 (NM_001128142) has the longest exon 3, lacks exons 2 and 4, and encodes the shortest isoform. The variant 3 (NM_001199682) does not include exon 2 and has the shortest exon 3. The RSUME mRNA transcripts variants 1, 2 and 3 codify for RSUME isoforms of 267, 195 and 200 aminoacids, named RSUME267, RSUME195 and RSUME200, respectively (Fig. 1). The non-coding RNA (NR_037643) contains all the exons but presents a premature stop codon in the exon 2 that leads it to degradation via NMD. Because of this, such variant does not encode any protein.

Bottom Line: Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain.We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME.The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET, Buenos Aires, Argentina.

ABSTRACT
RSUME (RWD-containing SUMO Enhancer) is a small protein that increases SUMO conjugation to proteins. To date, four splice variants that codify three RSUME isoforms have been described, which differ in their C-terminal end. Comparing the structure of the RSUME isoforms we found that, in addition to the previously described RWD domain in the N-terminal, all these RSUME variants also contain an intermediate domain. Only the longest RSUME isoform presents a C-terminal domain that is absent in the others. Given these differences, we used the shortest and longest RSUME variants for comparative studies. We found that the C-terminal domain is dispensable for the SUMO-conjugation enhancer properties of RSUME. We also demonstrate that these two RSUME variants are equally induced by hypoxia. The NF-κB signaling pathway is inhibited and the HIF-1 pathway is increased more efficiently by the longest RSUME, by means of a greater physical interaction of RSUME267 with the target proteins. In addition, the mRNA and protein levels of these isoforms differ in human glioma samples; while the shortest RSUME isoform is expressed in all the tumors analyzed, the longest variant is expressed in most but not all of them. The results presented here show a degree of redundancy of the RSUME variants on the SUMO pathway. However, the increased inhibition conferred by RSUME267 over the NF-κB signaling pathway, the increased activation over the HIF-1 pathway and the different expression of the RSUME isoforms suggest specific roles for each RSUME isoform which may be relevant in certain types of brain tumors that express RSUME, like human pituitary adenomas and gliomas.

Show MeSH
Related in: MedlinePlus