https://orcid.org/0000-0002-7414-2285
Figures & data
Table 1. Main RBPs associated with ARE sequences (for extended list see [Citation145]).
Figure 1. Involvement of RBPs in senescence-associated secretory phenotype (SASP).
Exogenous (cigarette smoke) and endogenous (ROS/RNS, inflammation, genetic predisposition) factors trigger changes in cellular phenotypes regulated by transcriptional and post-transcriptional events, coordinated by stress-induced signaling pathways. Exemplary of post-transcriptional events, mTOR activation via PI3K signaling leads to the inhibition of sirtuin-1 and sirtuin-6 through miR-34a upregulation, along with the downregulation of mRNA degrading activity of the RBP ZFP36L1 via MAPKAPK2-mediated phosphorylation. PI3K signaling also acts as inhibitor of the RBP TTP. DNA damage induced by stress conditions results in cell cycle arrest as a consequence of the activation of cyclin-dependent kinase inhibitors p16INK and p21CIP1, negatively regulated by the RBPs AUF-1 and TTP.
Upon these conditions, targeted cells acquire SASP resulting in the secretion of multiple inflammatory cytokines, chemokines, proteins, growth factors vastly regulated by RBPs (short-listed in the figure), though complex changes in mRNA stability and translation. Among the RBPs characterized in these processes, HuR has been reported to act globally as a positive regulator while AUF-1, TTP and ZFP36L1 generally decrease mRNA stability. AUF-1 has also regulatory roles in transcription. Dysregulation of SASP factors leads to the development of COPD and lung cancer. See discussion [Citation52, Citation53]. Created with BioRender.com.
Abbreviations: AMPK: AMP-activated protein kinase; AUF-1: AU-rich element binding factor 1; CCL: C-C motif ligand; COPD: chronic obstructive pulmonary disease; CXCL: C-X-C motif ligand; HuR: human antigen R; IL: interleukin; MAPKAPK2: mitogen-activated protein kinase-activated protein kinase 2; miR: microRNA; MMP: matrix metalloproteinase; mTOR: mechanistic target of rapamycin; PI3K: phosphatidylinositol 3-kinase; PTEN: phosphatase and TENsin homolog; RBP: RNA binding protein; ROS: reactive oxygen species; RNS: reactive nitrogen species; SASP: Senescence-associated secretory phenotype; TGF: transforming growth factor; TNF: tumor necrosis factor; TTP: tristetraprolin; VEGF: vascular endothelial growth factor A; ZFP36 L1 Zinc finger protein 36 -like 1.
![Figure 1. Involvement of RBPs in senescence-associated secretory phenotype (SASP).Exogenous (cigarette smoke) and endogenous (ROS/RNS, inflammation, genetic predisposition) factors trigger changes in cellular phenotypes regulated by transcriptional and post-transcriptional events, coordinated by stress-induced signaling pathways. Exemplary of post-transcriptional events, mTOR activation via PI3K signaling leads to the inhibition of sirtuin-1 and sirtuin-6 through miR-34a upregulation, along with the downregulation of mRNA degrading activity of the RBP ZFP36L1 via MAPKAPK2-mediated phosphorylation. PI3K signaling also acts as inhibitor of the RBP TTP. DNA damage induced by stress conditions results in cell cycle arrest as a consequence of the activation of cyclin-dependent kinase inhibitors p16INK and p21CIP1, negatively regulated by the RBPs AUF-1 and TTP.Upon these conditions, targeted cells acquire SASP resulting in the secretion of multiple inflammatory cytokines, chemokines, proteins, growth factors vastly regulated by RBPs (short-listed in the figure), though complex changes in mRNA stability and translation. Among the RBPs characterized in these processes, HuR has been reported to act globally as a positive regulator while AUF-1, TTP and ZFP36L1 generally decrease mRNA stability. AUF-1 has also regulatory roles in transcription. Dysregulation of SASP factors leads to the development of COPD and lung cancer. See discussion [Citation52, Citation53]. Created with BioRender.com.Abbreviations: AMPK: AMP-activated protein kinase; AUF-1: AU-rich element binding factor 1; CCL: C-C motif ligand; COPD: chronic obstructive pulmonary disease; CXCL: C-X-C motif ligand; HuR: human antigen R; IL: interleukin; MAPKAPK2: mitogen-activated protein kinase-activated protein kinase 2; miR: microRNA; MMP: matrix metalloproteinase; mTOR: mechanistic target of rapamycin; PI3K: phosphatidylinositol 3-kinase; PTEN: phosphatase and TENsin homolog; RBP: RNA binding protein; ROS: reactive oxygen species; RNS: reactive nitrogen species; SASP: Senescence-associated secretory phenotype; TGF: transforming growth factor; TNF: tumor necrosis factor; TTP: tristetraprolin; VEGF: vascular endothelial growth factor A; ZFP36 L1 Zinc finger protein 36 -like 1.](/cms/asset/8249fecb-eb10-428a-8267-bfc2285b87b9/icop_a_2107500_f0001_c.jpg)
Table 2. SASP factors transcripts regulated by RBPs.