RESUMO
Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , MicroRNAs , Neoplasias , Doenças do Sistema Nervoso , RNA Circular , RNA Neoplásico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Humanos , MicroRNAs/biossíntese , MicroRNAs/genética , Neoplasias/genética , Neoplasias/metabolismo , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismo , RNA Circular/biossíntese , RNA Circular/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genéticaRESUMO
Over the last decades, it has become evident that highly complex networks of regulators govern post-transcriptional regulation of gene expression. A novel class of Argonaute (Ago)-associated RNA molecules, the agotrons, was recently shown to function in a Drosha- and Dicer-independent manner, hence bypassing the maturation steps required for canonical microRNA (miRNA) biogenesis. Agotrons are found in most mammals and associate with Ago as â¼100 nucleotide (nt) long RNA species. Here, we speculate on the functional and biological relevance of agotrons: (i) agotrons could serve as non-promiscuous miRNA-like regulators with reduced off-targeting or (ii) agotrons could encompass other putative functions, such as protecting Ago proteins from taking up aberrant short RNAs or by rescuing and stabilizing otherwise unloaded Ago-proteins from degradation. Collectively, agotrons have emerged as a novel class of interesting non-coding RNA molecules, but their full functional potential and biological impact still remain to be disclosed.
