G-CSF factor stem-loop destabilising element: Difference between revisions

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{{Infobox rfam

{{Rfam_box|acc=RF00183|description=G-CSF factor stem-loop destabilising element (SLDE)|abbreviation=G-CSF_SLDE|type=Cis-reg;|avg_length=94.2|avg_identity=86|ss=Published; {{PMID|11865046}}|se={{PMID|11865046}}|type=Cis-reg;}}

| Name = G-CSF factor stem-loop destabilising element (SLDE)

| image = RF00183.jpg

| width =

| caption = Predicted [[secondary structure]] and [[sequence conservation]] of G-CSF_SLDE

| Symbol = G-CSF_SLDE

| AltSymbols =

| Rfam = RF00183

| miRBase =

| miRBase_family =

| RNA_type = [[Cis-regulatory element|Cis-reg]]

| Tax_domain = [[Eukaryota]]

| GO =

| SO = {{SO|0000233}}

| CAS_number =

| EntrezGene =

| HGNCid =

| OMIM =

| PDB =

| RefSeq =

| Chromosome =

| Arm =

| Band =

| LocusSupplementaryData =

}}

The '''G-CSF factor stem-loop destabilising element (SLDE)''' is an [[cis-regulatory element|RNA element]] secreted by [[fibroblast]]s and [[endothelial cells]] in response to the inflammatory mediators [[interleukin-1]] (IL-1) and [[tumour necrosis factor -alpha]] and by activated macrophages[[macrophage]]s. The synthesis of G-CSF is regulated both [[transcription (genetics)|transcriptionally]] and through control of [[mRNA]] stability. In unstimulated cells G-CSF mRNA is unstable but becomes stabilised in response to IL-1 or tumour necrosis factor alpha, and also in the case of monocytes[[monocyte]]s and macrophages, in response to [[lipopolysaccharide]]. It is likely that the presence of the SLDE in the G-CSF mRNA contributes to the specificity of regulation of G-CSF mRNA and enhances the rate of shortening of the [[polyadenylation|poly(A) tail]].<ref>{{cite journal | lastvauthors = Putland | first = RA | coauthors =, Sassinis TA, Harvey JS, Diamond P, Coles LS, Brown CY, Goodall GJ | year = 2002 | title = RNA destabilization by the granulocyte colony-stimulating factor stem-loop destabilizing element involves a single stem-loop that promotes deadenylation | journal = MolMolecular Celland Cellular BiolBiology | volume = 22 | issue = 6 | pages = 1664&ndash;16731664–1673 | iddate = PMIDMarch 2002 | pmid = 11865046 | pmc = 135610 | doi = 10.1128/MCB.22.6.1664-1673.2002 }}</ref>

[[AU-rich element|Adenylate uridylate-rich elements]] (AUREs) are present in other cytokine mRNAs, but the SLDE is the most important element that stabilizes G-CSF mRNA in response to IL-1 or tumor necrosis factor- alpha.<ref>{{cite journal | vauthors = Brown CY, Lagnado CA, Goodall GJ | title = A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 24 | pages = 13721–13725 | date = November 1996 | pmid = 8943001 | pmc = 19403 | doi = 10.1073/pnas.93.24.13721 | bibcode = 1996PNAS...9313721B | doi-access = free }}</ref> Additionally, there are destabilizing elements similar to SLDE found in [[Interleukin 2|IL-2]] and [[Interleukin 6|IL-6]]. The 3'-UTR of G-CSF mRNA contains a destabilizing element that is insensitive to [[Calcium Ionophore A23187|calcium ionophore]], hence SLDE regulates G-CSF mRNA. AUDEs do not function in 5637 Bladder carcinoma cells, but the SLDE does. The two destablizing elements, SLDE and AURE, provide multiple mechanisms to regulate cytokine expression.

==Reference==

[[Neutrophil]]s, are the most abundant type of [[granulocyte]]s and are responsible for leading the first response of the immune system response against invaders. Granulocyte-colony stimulating factor (G-CSF) is a [[glycoprotein]] that stimulates proliferation of neutrophil [[progenitor cell]]s and leads to the maturation of neutrophils. [[monocyte]]s and [[macrophage]]s are the cells that secrete G-CSF, but it is found that [[Endothelium|endothelial cells]], [[Fibroblast|fibroblasts]], and [[Bone marrow|bone marrow stromal cells]] also secrete the glycoprotein. Expression of G-CSF glycoprotein is complex and has both transcription and post transcription regulation. Two specific types of [[Regulatory sequence|regulatory elements]] are present in the [[Three prime untranslated region|3' untranslated region]] (3'UTR) of G-CSF [[Messenger RNA|mRNA]]. These elements are referred to as adenylate uridylate-rich elements (AUREs) and stem-loop destabilizing element (SLDE). They have been shown to be destabilizing elements of the G-CSF mRNA. On the other hand, the stability of the mRNA is regulated by [[P38 mitogen-activated protein kinases|p38 mitogen-activated protein kinase]] (MAPK) and this phosphorylating enzyme has been shown to be linked to the AUREs in the 3'UTR.

{{reflist|1}}

SB203580 specifically inhibits the [[Catalysis|catalytic activity]] of p38 MAPK by competitively binding to the active site where [[ATP synthase|ATP]] is supposed to bind and is used to probe the role of p38 MAPK in cells.<ref>{{cite journal | vauthors = Chang SF, Li HC, Huang YP, Tasi WJ, Chou YY, Lu SC | title = SB203580 increases G-CSF production via a stem-loop destabilizing element in the 3' untranslated region in macrophages independently of its effect on p38 MAPK activity | journal = Journal of Biomedical Science | volume = 23 | issue = 1 | pages = 3 | date = January 2016 | pmid = 26772539 | pmc = 4715298 | doi = 10.1186/s12929-016-0221-z | doi-access = free }}</ref> SB203580 amplified the lipopolysaccharide-induced increase in the G-CSF mRNA levels in mouse [[Bone marrow-derived macrophage|bone marrow-derived macrophages]] and in THP-1 human macrophages. By displaying that the decay of G-CSF mRNA, in the presence of [[Dactinomycin|actinomycin D]], was slower in SB203580-treated cells. SB203580 increased the stability of G-CSF mRNA. SLDE is essential for the SB203580-induced increase in the stability of mRNA.{{short description|RNA element}}

==External link==

== References ==

{{reflist|1}}

== External linklinks ==

* {{Rfam|id=RF00183|name=G-CSF factor stem-loop destabilising element (SLDE)}}

{{molecular-cell-biology-stub}}

[[Category:Cis-regulatory RNA elements]]

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