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Figure 2 | Respiratory Research

Figure 2

From: Transposable elements and their potential role in complex lung disorder

Figure 2

a. Life cycle of L1 retrotransposon. i) Transcription; L1 life cycle starts with the transcription of active L1 in the genome by recruitment of transcription factors, followed by polyadenylation and splicing to form L1 RNA, which is nuclear exported. ii) Translation; Active L1RNA codes for the ORF1 and ORF2 protein that binds with other retrotranscription competent L1 (RC-L1) RNA to form L1RNP (Ribonucleoprotein) complex, which is nuclear imported for retrotransposition. iii) Insertional events; results in DSBs by the activity of L1 ORF2 endonuclease followed by, iv) integration; lesions created by L1ORF2 activity is repaired and integrated in to the genome by TPRT. v) Heavy metals and other smoke particles can interact with L1 lifecycle either at the early stages by altering the methylation profile (epigenetic alteration) resulting in active L1 or at the late repair stages by impairing repair pathway resulting in somatic mutation accumulation (Granulated cells). b.Effect of somatic mutation accumulation on disease onset and exacerbation. Mutated somatic cells are recognized by the host system as foreign cells and are presented by antigen presenting cells (APCs) triggering a cascade of pathways involving T helper cells (Th) and cytotoxic T cells (Tc), which migrates to the infected site and releases various transmitters inducing cell death. Failure in effective efferocytosis results in aberrant remodeling of the structure and the characteristic onset of COPD. Mutant cells can interact with transcription factors to increase the release of cytokines and the consequent recruitment of inflammatory cells thereby destabilizing the immune balance and manifest the features of COPD.

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