Abstract
There is a huge number of noncoding RNA (ncRNA) transcripts in the cell with important roles in modulation of different mechanisms. ANRIL is a long ncRNA with 3.8 kb length that is transcribed in the opposite direction of the INK4/ARF locus in chromosome 9p21. It was shown that polymorphisms within this locus are associated with vascular disorders, notably coronary artery disease (CAD), which is considered as a risk factor for life-threatening events like myocardial infarction and stroke. ANRIL is subjected to a variety of splicing patterns producing multiple isoforms. Linear isoforms could be further transformed into circular ones by back-splicing. ANRIL regulates genes in atherogenic network in a positive or negative manner. This regulation is implemented both locally and remotely. While CAD is known as a proliferative disorder and cell proliferation plays a crucial role in the progression of atherosclerosis, the functions of ANRIL and CAD development are intertwined remarkably. This makes ANRIL a suitable target for diagnostic, prognostic, and even therapeutic aims. In this review, we tried to present a comprehensive appraisal on different aspects of ANRIL including its location, structure, isoforms, expression, and functions. In each step, the contribution of ANRIL to atherosclerosis is discussed.
Highlights
Coronary artery disease (CAD) has been become the leading cause of hospitalization and death in the era of cardiovascular disorders [1]
Novel circular ANRIL isoforms have been identified whose expression levels are in association with transcription level of the INK4/ARF locus, and they are in close relation with atherosclerosis risk [36]
Specific transcription of ANRIL in each cell type regulates specific sequels in the cellular processes. Another level of regulation is implemented through splicing that leads to multiple varieties and dissimilar ANRIL abundance in different cell types [32]
Summary
Coronary artery disease (CAD) has been become the leading cause of hospitalization and death in the era of cardiovascular disorders [1]. The length of lncRNAs is about more than 200 nucleotides [5] Researchers thought that they are only a kind of transcriptional noise, but later, it was revealed that they are able to regulate different biological mechanisms. They are means of information transport between cells [6–8]. LncRNAs are much more complex than microRNAs regarding their functions like gene regulation, either positive or negative, altering chromatin structure, and contribution to developmental processes [9, 10] This type of RNAs implicates in several physiological and pathological processes such as cell growth and inflammation as well as regulation of cardiac development [5, 11–15]. Large unknown avenues in this area prompted us to present a comprehensive appraisal on different perspectives of ANRIL including its locus, exons, isoforms, expression, abundance, and functions in relation to atherosclerosis
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