SASP regulation by noncoding RNA

Abstract

Noncoding RNAs (ncRNAs), including micro (mi)RNAs, long noncoding (lnc)RNAs, and circular (circ)RNAs, control specific gene expression programs by regulating transcriptional, post-transcriptional, and post-translational processes. Through their broad influence on protein expression and function, ncRNAs have been implicated in virtually all cellular processes such as proliferation, senescence, quiescence, differentiation, apoptosis, and the stress and immune responses. Senescence is a cellular phenotype associated with the physiologic decline of aging and with age-related pathologies. Besides their characteristic terminal growth arrest and differential gene expression programs, senescent cells are known to secrete potent pro-inflammatory, angiogenic, and tissue-remodeling factors. This important trait, known as the senescence-associated secretory phenotype (SASP), influences many biological processes such as tissue repair and regeneration, tumorigenesis, and the aging-associated pro-inflammatory state. Here, we review the microRNAs, lncRNAs, and circRNAs that influence the production of SASP factors and discuss the rising interest in SASP-regulatory ncRNAs as diagnostic and therapeutic targets.

The emerging role of alternative splicing in senescence and aging

“…Another group of potentially relevant regulatory molecules are noncoding RNAs. Some display age‐dependent changes in expression (e.g., see Gruner et al ., ), and recent studies have implicated microRNAs, large noncoding RNAs, and circular RNAs in senescence and SASP (Abdelmohsen & Gorospe, ; Panda et al ., ). Specifically, the circular RNA CircPVT1, whose expression is reduced in senescent cells, is produced by circularization of an exon of the PVT gene through RNA splicing.…”

Markers of T Cell Senescence in Humans

“…Lipid and nicotinamide (NAD) metabolism are also two other features of mitochondria that could be associated with cellular senescence as they are correlated with age-related diseases [ 95 , 96 , 97 , 98 ] Besides mitochondria, studies have investigated at the RNA level and assessed the role of non-coding RNA (i.e., micro RNAs, long noncoding RNAa and circular RNAs) with cellular senescence in aging organs/tissue. [ 99 , 100 , 101 , 102 ]. On the epigenetic level, CD4 and CD8 T cells have been shown to have an overall decrease in methylation as they progressed from Naïve to TE [ 103 , 104 ].…”

SCAMP4 enhances the senescent cell secretome

“…These inducers activate prominent transcriptional regulators of SASP factor production in senescent cells, notably NF-κB and C/EBPβ, which induce the transcription of SASP genes such as IL6 and IL8 (Orjalo et al 2009). At the post-transcriptional level, numerous regulators of the stability and translation of mRNAs encoding SASP factors have also been identified, including several RNA-binding proteins (e.g., ILF3/NF-90), microRNAs (e.g., miR-146a/b, miR-335, miR-15b, and miR-34a), long noncoding RNAs (e.g., THRIL, NEAT1, Lethe, etc), and circular RNAs (e.g., CircPVT1 and Circ-Foxo3) (Tominaga-Yamanaka et al 2012;Steri et al 2017; for review, see Panda et al 2017). However, the mechanisms by which cytokines are secreted by senescent cells are not well understood, although there is evidence that they include exocytosis, direct protein secretion, and secretion via vesicles such as exosomes.…”