SASP regulation by noncoding RNA.

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.

Panda AC ，Abdelmohsen K ，Gorospe M 《-》

Noncoding RNAs in Cardiovascular Aging.

Li Y ，Zhu Y ，Li G ，Xiao J ... -  《Advances in Experimental Medicine and Biology》

Non-coding RNAs derailed: The many influences on the fatty acid reprogramming of cancer.

Non-coding RNAs (NcRNAs), a family of functional RNA molecules that cannot translate into proteins but control specific gene expression programs, have been shown to be implicated in various biological processes, including fatty acid metabolism. Fast-growing tumor cells rewire their fatty acid metabolic circuitry in order to meet the needs of energy storage, membrane proliferation, and the generation of signaling molecules, which is achieved by regulating a variety of key enzymes along with related signaling pathways in fatty acid metabolism. This review presents an update of our knowledge about the regulatory network of ncRNAs-specifically, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs)-in this metabolic shift and discusses the possibility of ncRNA-based therapeutics being applied to the restoration of cancer-related fatty acid metabolism.

Yu XH ，Wang HF ，Wu JB ，Wang SS ，Tang YJ ，Tang YL ，Liang XH ... -  《-》

Noncoding RNA control of cellular senescence.

Senescent cells accumulate in normal tissues with advancing age and arise by long-term culture of primary cells. Senescence develops following exposure to a range of stress-causing agents and broadly influences the physiology and pathology of tissues, organs, and systems in the body. While many proteins are known to control senescence, numerous noncoding (nc)RNAs are also found to promote or repress the senescent phenotype. Here, we review the regulatory ncRNAs (primarily microRNAs and lncRNAs) identified to-date as key modulators of senescence. We highlight the major senescent pathways (p53/p21 and pRB/p16), as well as the senescence-associated secretory phenotype (SASP) and other senescence-associated events governed by ncRNAs, and discuss the importance of understanding comprehensively the ncRNAs implicated in cell senescence.

Abdelmohsen K ，Gorospe M 《-》

Genome-Wide Dynamics of Nascent Noncoding RNA Transcription in Porcine Heart After Myocardial Infarction.

Microarrays and RNA sequencing are widely used to profile transcriptome remodeling during myocardial ischemia. However, the steady-state RNA analysis lacks in sensitivity to detect all noncoding RNA species and does not provide separation between transcriptional and post-transcriptional regulations. Here, we provide the first comprehensive analysis of nascent RNA profiles of mRNAs, primary micro-RNAs, long noncoding RNAs, and enhancer RNAs in a large animal model of acute infarction. Acute infarction was induced by cardiac catheterization of domestic swine. Nuclei isolated from healthy, border zone, and ischemic regions of the affected heart were subjected to global run-on sequencing. Global run-on sequencing analysis indicated that half of affected genes are regulated at the level of transcriptional pausing. A gradient of induction of inflammatory mediators and repression of peroxisome proliferator-activated receptor signaling and oxidative phosphorylation was detected when moving from healthy toward infarcted area. In addition, we interrogated the transcriptional regulation of primary micro-RNAs and provide evidence that several arrhythmia-related target genes exhibit repression at post-transcriptional level. We identified 450 long noncoding RNAs differently regulated by ischemia, including novel conserved long noncoding RNAs expressed in antisense orientation to myocardial transcription factors GATA-binding protein 4, GATA-binding protein 6, and Krüppel-like factor 6. Finally, characterization of enhancers exhibiting differential expression of enhancer RNAs pointed a central role for Krüppel-like factor, MEF2C, ETS, NFY, ATF, E2F2, and NRF1 transcription factors in determining transcriptional responses to ischemia. Global run-on sequencing allowed us to follow the gradient of gene expression occurring in the ischemic heart and identify novel noncoding RNAs regulated by oxygen deprivation. These findings highlight potential new targets for diagnosis and treatment of myocardial ischemia.

Kaikkonen MU ，Halonen P ，Liu OH ，Turunen TA ，Pajula J ，Moreau P ，Selvarajan I ，Tuomainen T ，Aavik E ，Tavi P ，Ylä-Herttuala S ... -  《-》