The piRNA Pathway Guards the Germline Genome Against Transposable Elements

Transposable elements (TEs) have the capacity to replicate and insert into new genomic locations. This contributs significantly to evolution of genomes, but can also result in DNA breaks and illegitimate recombination, and therefore poses a significant threat to genomic integrity. Excess damage to the germ cell genome results in sterility. A specific RNA silencing pathway, termed the piRNA pathway operates in germ cells of animals to control TE activity. At the core of the piRNA pathway is a ribonucleoprotein complex consisting of a small RNA, called piRNA, and a protein from the PIWI subfamily of Argonaute nucleases. The piRNA pathway relies on the specificity provided by the piRNA sequence to recognize complementary TE targets, while effector functions are provided by the PIWI protein. PIWI-piRNA complexes silence TEs both at the transcriptional level – by attracting repressive chromatin modifications to genomic targets – and at the posttranscriptional level – by cleaving TE transcripts in the cytoplasm. Impairment of the piRNA pathway leads to overexpression of TEs, significantly compromised genome structure and, invariably, germ cell death and sterility. The piRNA pathway is best understood in the fruit fly, Drosophila melanogaster, and in mouse. This Chapter gives an overview of current knowledge on piRNA biogenesis, and mechanistic details of both transcriptional and posttranscriptional TE silencing by the piRNA pathway. It further focuses on the importance of post-translational modifications and subcellular localization of the piRNA machinery. Finally, it provides a brief description of analogous pathways in other systems

Promising biomolecules

The osteochondral defect (OD) comprises the articular cartilage and its subchondral bone. The treatment of these lesions remains as one of the most problematic clinical issues, since these defects include different tissues, requiring distinct healing approaches. Among the growing applications of regenerative medicine, clinical articular cartilage repair has been used for two decades, and it is an effective example of translational medicine; one of the most used cell-based repair strategies includes implantation of autologous cells in degradable scaffolds such as alginate, agarose, collagen, chitosan, chondroitin sulfate, cellulose, silk fibroin, hyaluronic acid, and gelatin, among others. Concerning the repair of osteochondral defects, tissue engineering and regenerative medicine started to design single- or bi-phased scaffold constructs, often containing hydroxyapatite-collagen composites, usually used as a bone substitute. Biomolecules such as natural and synthetic have been explored to recreate the cartilage-bone interface through multilayered biomimetic scaffolds. In this chapter, a succinct description about the most relevant natural and synthetic biomolecules used on cartilage and bone repair, describing the procedures to obtain these biomolecules, their chemical structure, common modifications to improve its characteristics, and also their application in the biomedical fields, is given.(undefined)info:eu-repo/semantics/publishedVersio