The heterodimeric cytokine interleukin-23 (IL-23 or IL23A/IL12B) is produced by dendritic cells and macrophages and promotes the proinflammatory and regenerative activities of T helper 17 (Th17) and innate lymphoid cells. A recent study has reported that IL-23 is also secreted by lung adenoma cells and generates an inflammatory and immune-suppressed stroma. Here, we observed that proinflammatory tumor necrosis factor (TNF)/NF-κB and mitogen-activated protein kinase (MAPK) signaling strongly induce IL23A expression in intestinal epithelial cells. Moreover, we identified a strong crosstalk between the NF-κB and MAPK/ERK kinase (MEK) pathways, involving the formation of a transcriptional enhancer complex consisting of proto-oncogene c-Jun (c-Jun), RELA proto-oncogene NF-κB subunit (RelA), RUNX family transcription factor 1 (RUNX1), and RUNX3. Collectively, these proteins induced IL23A secretion, confirmed by immunoprecipitation of endogenous IL23A from activated human colorectal cancer (CRC) cell culture supernatants. Interestingly, IL23A was likely secreted in a noncanonical form, as it was not detected by an ELISA specific for heterodimeric IL-23 likely because IL12B expression is absent in CRC cells. Given recent evidence that IL23A promotes tumor formation, we evaluated the efficacy of MAPK/NF-κB inhibitors in attenuating IL23A expression and found that the MEK inhibitor trametinib and BAY 11–7082 (an IKKα/IκB inhibitor) effectively inhibited IL23A in a subset of human CRC lines with mutant KRAS or BRAFV600E mutations. Together, these results indicate that proinflammatory and mitogenic signals dynamically regulate IL23A in epithelial cells. They further reveal its secretion in a noncanonical form independent of IL12B and that small-molecule inhibitors can attenuate IL23A secretion.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

Charles Collot, Frank Merle and Pierre Raphaël
J. Amer. Math. Soc. 33 (2020), 527-607.
Abstract, references and article information

Pierre Lairez
J. Amer. Math. Soc. 33 (2019), 487-526.
Abstract, references and article information

Dawid Kielak
J. Amer. Math. Soc. 33 (2019), 451-486.
Abstract, references and article information

Viviane Baladi and Mark F. Demers
J. Amer. Math. Soc. 33 (2020), 381-449.
Abstract, references and article information

Yves André
J. Amer. Math. Soc. 33 (2020), 363-380.
Abstract, references and article information

Pierre Colmez, Gabriel Dospinescu and Wiesława Nizioł
J. Amer. Math. Soc. 33 (2019), 311-362.
Abstract, references and article information

N. Leigh Anderson
Apr 1, 2004; 3:311-326
Research

Myriam Ferro
May 1, 2003; 2:325-345
Research

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research

Marilyn Goudreault
Jan 1, 2009; 8:157-171
Research

Joe Carroll
Feb 1, 2003; 2:117-126
Research

Alfred C. O. Vertegaal
Dec 1, 2006; 5:2298-2310
Research

Junmei Zhang
Feb 1, 2009; 8:215-225
Research

Roland Bruderer
May 1, 2015; 14:1400-1410
Research

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources

Yue Chen
May 1, 2007; 6:812-819
Research

Boris Macek
Feb 1, 2008; 7:299-307
Research

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research

Ivan Matic
Jan 1, 2008; 7:132-144
Research

Ileana M. Cristea
Dec 1, 2005; 4:1933-1941
Research

M. Wang
Aug 1, 2012; 11:492-500
Technological Innovation and Resources

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research

Qin Liu
Aug 1, 2007; 6:1299-1317
Research

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research

Lawrence E. Ostrowski
Jun 1, 2002; 1:451-465
Research

Sean R. Collins
Mar 1, 2007; 6:439-450
Research

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research

Guoan Chen
Apr 1, 2002; 1:304-313
Research

Qiang Tian
Oct 1, 2004; 3:960-969
Research

Jesper V. Olsen
Jun 1, 2004; 3:608-614
Technology

Alexey I. Nesvizhskii
Oct 1, 2005; 4:1419-1440
Tutorial

Ludovic C. Gillet
Jun 1, 2012; 11:O111.016717-O111.016717
Research

Yu Xue
Sep 1, 2008; 7:1598-1608
Research

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
Research

Mathias Uhlén
Dec 1, 2005; 4:1920-1932
Research

William M. Old
Oct 1, 2005; 4:1487-1502
Research

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology

Jeffrey C. Silva
Jan 1, 2006; 5:144-156
Research

N. Leigh Anderson
Nov 1, 2002; 1:845-867
Reviews/Perspectives