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

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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 [[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 [[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 | vauthors = Putland RA, Sassinis TA, Harvey JS, Diamond P, Coles LS, Brown CY, Goodall GJ | title = RNA destabilization by the granulocyte colony-stimulating factor stem-loop destabilizing element involves a single stem-loop that promotes deadenylation | journal = Molecular and Cellular Biology | volume = 22 | issue = 6 | pages = 1664–1673 | date = March 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 | 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.

[[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.