Butyrate mediated regulation of RNA binding proteins in the post-transcriptional regulation of inflammatory gene expression

Date

2019-12-01

Author

Torun, Aydan
Enayat, Shabnam
Sheraj, Ilir
Tuncer, Sinem
Ulgen, Dogukan Hazar
Banerjee, Sreeparna

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

250
views

0
downloads

Short chain fatty acids (SCFAs) are produced by commensal bacteria in the gut and are known to reduce inflammation through transcriptional inhibition of cytokines and inflammatory proteins such as cyclooxygenase-2 (COX-2). Butyrate is a SCFA that was reported to alter the mRNA stability of inflammatory genes by increasiing the expression of the RNA binding protein (RBP) Tristetraprolin (TTP). We have hypothesized that butyrate may regulate gene expression post-transcriptionally through global effects on the expression or cytoplasmic trans location of RBPs. Using bioinformatics analyses of publicly available microarray data as well as colon cancer cell lines treated with sodium butyrate, we have observed that butyrate treatment led to a general reduction in expression of several (but not all) RBPs and inhibition in the cytosolic translocation of HuR, a well-known stabilizing RBP. This was reflected in reduced NanoLuc reporter activity of several different AU-rich element (ARE) sequences in the presence of butyrate; this suppression was retained even when HuR was overexpressed. Mechanistically, we have shown that reduced activity of HuR was related to decreased phosphorylation of p38 and MK2 and enhanced phosphorylation of Chk2. As a proof of concept, we show butyrate-mediated inhibition in binding of HuR to the 3'UTR of COX-2 mRNA resulting in reduced mRNA and protein levels of the inflammatory gene. Overall, our data suggest that butyrate can reduce the expression of inflammatory genes not only by transcriptional regulation, but also by post-transcriptional regulation via inhibition of mRNA stabilizing proteins.

Subject Keywords

Cell Biology

URI

https://hdl.handle.net/11511/48374

Journal

CELLULAR SIGNALLING

DOI

https://doi.org/10.1016/j.cellsig.2019.109410

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

The NF-kappa B target genes ICAM-1 and VCAM-1 are differentially regulated during spontaneous differentiation of Caco-2 cells Astarci, Erhan; Sade, Asli; Cimen, Ismail; SAVAŞ, BERNA; Banerjee, Sreeparna (Wiley, 2012-08-01) Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cellcell and cellmicroenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line, which undergoes spontaneous re-differentiation when grown past confluency, we observed a loss of VCAM-1 (vascular cell adhesion molecule 1) mRNA expression, while ICAM-1 (intercellular cell adhesion m...
Emerging cellular functions of the lipid metabolizing enzyme 15-Lipoxygenase-1 Colakoglu, Melis; Tuncer, Sinem; Banerjee, Sreeparna (Wiley, 2018-10-01) The oxygenation of polyunsaturated fatty acids such as arachidonic and linoleic acid through lipoxygenases (LOXs) and cyclooxygenases (COXs) leads to the production of bioactive lipids that are important both in the induction of acute inflammation and its resolution. Amongst the several isoforms of LOX that are expressed in mammals, 15-LOX-1 was shown to be important both in the context of inflammation, being expressed in cells of the immune system, and in epithelial cells where the enzyme has been shown to...
Drug repositioning as an effective therapy for protease-activated receptor 2 inhibition Saqib, Uzma; Savai, Rajkumar; Liu, DongFang; Banerjee, Sreeparna; Baig, Mirza S. (Wiley, 2019-02-01) Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor activated by both trypsin and a specific agonist peptide, SLIGKV-NH2. It has been linked to various pathologies, including pain and inflammation. Several peptide and peptidomimetic agonizts for PAR-2 have been developed exhibiting high potency and efficacy. However, the number of PAR-2 antagonists is smaller. We screened the Food and Drug Administration library of approved compounds to retrieve novel antagonists for repositioning in the...
Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery. Kiriş, Erkan; Burnett, JC; Kota, KP; Koh, DC; Wanner, LM; Torres-Melendez, E; Gussio, R; Tessarollo, L; Bavari, S (Elsevier BV, 2011-05-01) Botulinum neurotoxins (BoNTs) inhibit cholinergic synaptic transmission by specifically cleaving proteins that are crucial for neurotransmitter exocytosis. Due to the lethality of these toxins, there are elevated concerns regarding their possible use as bioterrorism agents. Moreover, their widespread use for cosmetic purposes, and as medical treatments, has increased the potential risk of accidental overdosing and environmental exposure. Hence, there is an urgent need to develop novel modalities to counter ...
15-lipoxygenase-1 exerts its tumor suppressive role by inhibiting nuclear factor-kappa B via activation of PPAR gamma. Cimen, I; Astarci, E; Banerjee, Sreeparna (Wiley, 2011-09-01) 15-Lipoxygenase-1 (15-LOX-1) is an enzyme of the inflammatory eicosanoid pathway whose expression is known to be lost in colorectal cancer (CRC). We have previously shown that reintroduction of the gene in CRC cell lines slows proliferation and induces apoptosis (Cimen et al. [2009] Cancer Sci 100: 2283-2291). We have hypothesized that 15-LOX-1 may be anti-tumorigenic by the inhibition of the antiapoptotic inflammatory transcription factor nuclear factor kappa B. We show here that ectopic expression of 15-L...

Citation Formats

A. Torun, S. Enayat, I. Sheraj, S. Tuncer, D. H. Ulgen, and S. Banerjee, “Butyrate mediated regulation of RNA binding proteins in the post-transcriptional regulation of inflammatory gene expression,” CELLULAR SIGNALLING, pp. 0–0, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/48374.