RESUMO
Functions of many long noncoding RNAs (lncRNAs) depend on their ability to interact with multiple copies of specific RNA-binding proteins (RBPs). Here, we devised a workflow combining bioinformatics and experimental validation steps to systematically identify RNAs capable of multivalent RBP recruitment. This uncovered a number of previously unknown transcripts encoding high-density RBP recognition arrays within genetically normal short tandem repeats. We show that a top-scoring hit in this screen, lncRNA PNCTR, contains hundreds of pyrimidine tract-binding protein (PTBP1)-specific motifs allowing it to sequester a substantial fraction of PTBP1 in a nuclear body called perinucleolar compartment. Importantly, PNCTR is markedly overexpressed in a variety of cancer cells and its downregulation is sufficient to induce programmed cell death at least in part by stimulating PTBP1 splicing regulation activity. This work expands our understanding of the repeat-containing fraction of the human genome and illuminates a novel mechanism driving malignant transformation of cancer cells.
Assuntos
Processamento Alternativo/fisiologia , Ribonucleoproteínas Nucleares Heterogêneas/fisiologia , Proteína de Ligação a Regiões Ricas em Polipirimidinas/fisiologia , Proteínas de Ligação a RNA/fisiologia , Processamento Alternativo/genética , Linhagem Celular , Movimento Celular , Núcleo Celular , Proliferação de Células , Sobrevivência Celular , Biologia Computacional/métodos , Éxons , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Repetições de Microssatélites/genética , Repetições de Microssatélites/fisiologia , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Pirimidinas , Splicing de RNA , RNA Longo não Codificante/fisiologiaRESUMO
Introduction. Acalculous cholecystitis in the setting of typhoid fever in adults is an infrequent clinical encounter, reported sparsely in the literature. In this case report we review the presentation and management of enteric fever involving the biliary system and consider the literature surrounding this topic. The aim of this case report is to alert clinicians to the potential diagnosis of extraintestinal complications in the setting of typhoid fever in the returned traveller, requiring surgical intervention. Presentation of Case. We report the case of a 23-year-old woman with acalculous cholecystitis secondary to Salmonella Typhi. Discussion. There is scarce evidence surrounding the optimal treatment and prognosis of typhoidal acalculous cholecystitis. In the current case, surgical invention was favoured due to failure of medical management. Conclusion. Clinical judgement dictated surgical intervention in this case of typhoidal acute acalculous cholecystitis, and cholecystectomy was safely performed.