PDF(Pubmed)
Abstract：
BACKGROUND: Concurrent existence of lncRNA and circular RNA at both nucleus and cytosol within a cell at different proportions is well reported. Previous studies showed that circular RNAs are synthesized in nucleus followed by transportation across the nuclear membrane and the export is primarily defined by their length. lncRNAs primarily originated through inefficient splicing and seem to use NXF1 for cytoplasm export. However, it is not clear whether circularization of lncRNA happens only in nucleus or it also occurs in cytoplasm. Studies indicate that circular RNAs arise when the splicing apparatus undergoes a phenomenon of back splicing. Minor spliceosome (U12 type) mediated splicing occurs in cytoplasm and is responsible for the splicing of 0.5% of introns of human cells. Therefore, possibility of cRNA biogenesis mediated by minor spliceosome at cytoplasm cannot be ruled out. Secondly, information on genes transcribing both circular and lncRNAs along with total number of RBP binding sites for both of these RNA types is extractable from databases. This study showed how these apparently unconnected pieces of reports could be put together to build a model for exploring biogenesis of circular RNA.
RESULTS: As a result of this study, a model was built under the premises that, sequences with special semantics were molecular precursors in biogenesis of circular RNA which occurred through catalytic role of some specific RBPs. The model outcome was further strengthened by fulfillment of three logical lemmas which were extracted and assimilated in this work using a novel data analytic approach, Integrated Cellular Geography. Result of the study was found to be in well agreement with proposed model. Furthermore this study also indicated that biogenesis of circular RNA was a post-transcriptional event.
CONCLUSIONS: Overall, this study provides a novel systems biology based model under the paradigm of Integrated Cellular Geography which can assimilate independently performed experimental results and data published by global researchers on RNA biology to provide important information on biogenesis of circular RNAs considering lncRNAs as precursor molecule. This study also suggests the possible RBP-mediated circularization of RNA in the cytoplasm through back-splicing using minor spliceosome.
RESULTS: As a result of this study, a model was built under the premises that, sequences with special semantics were molecular precursors in biogenesis of circular RNA which occurred through catalytic role of some specific RBPs. The model outcome was further strengthened by fulfillment of three logical lemmas which were extracted and assimilated in this work using a novel data analytic approach, Integrated Cellular Geography. Result of the study was found to be in well agreement with proposed model. Furthermore this study also indicated that biogenesis of circular RNA was a post-transcriptional event.
CONCLUSIONS: Overall, this study provides a novel systems biology based model under the paradigm of Integrated Cellular Geography which can assimilate independently performed experimental results and data published by global researchers on RNA biology to provide important information on biogenesis of circular RNAs considering lncRNAs as precursor molecule. This study also suggests the possible RBP-mediated circularization of RNA in the cytoplasm through back-splicing using minor spliceosome.
摘要：
背景：据报道，细胞内细胞核和细胞溶质中同时存在不同比例的lncRNA和环状RNA。先前的研究表明，环状RNA在细胞核中合成，然后通过核膜运输，并且输出主要由它们的长度定义。lncRNAs主要起源于低效的剪接，似乎使用NXF1进行细胞质输出。然而,尚不清楚lncRNA的环化是否仅发生在细胞核中，还是也发生在细胞质中。研究表明，当剪接装置经历反向剪接现象时，会出现环状RNA。小剪接体（U12型）介导的剪接发生在细胞质中，负责人类细胞0.5％内含子的剪接。因此,不能排除由细胞质中的次要剪接体介导的cRNA生物发生的可能性。其次,有关转录环状和lncRNAs的基因以及这两种RNA类型的RBP结合位点总数的信息可从数据库中提取。这项研究表明，如何将这些看似无关的报告放在一起，以建立探索环状RNA生物发生的模型。
结果：作为这项研究的结果，在前提下建造了一个模型，具有特殊语义的序列是通过某些特定RBPs的催化作用发生的环状RNA生物合成的分子前体。通过实现三个逻辑引理，使用新颖的数据分析方法在这项工作中提取和吸收，进一步加强了模型结果。综合细胞地理。研究结果与所提出的模型非常吻合。此外，这项研究还表明环状RNA的生物发生是转录后事件。
结论：总体而言，这项研究在整合细胞地理学范式下提供了一种基于系统生物学的新模型，该模型可以吸收全球RNA生物学研究人员独立执行的实验结果和发表的数据，以提供有关将lncRNAs作为前体分子的环状RNAs生物发生的重要信息。这项研究还表明，通过使用次要剪接体的反向剪接，RBP介导的RNA在细胞质中的环化可能。
结果：作为这项研究的结果，在前提下建造了一个模型，具有特殊语义的序列是通过某些特定RBPs的催化作用发生的环状RNA生物合成的分子前体。通过实现三个逻辑引理，使用新颖的数据分析方法在这项工作中提取和吸收，进一步加强了模型结果。综合细胞地理。研究结果与所提出的模型非常吻合。此外，这项研究还表明环状RNA的生物发生是转录后事件。
结论：总体而言，这项研究在整合细胞地理学范式下提供了一种基于系统生物学的新模型，该模型可以吸收全球RNA生物学研究人员独立执行的实验结果和发表的数据，以提供有关将lncRNAs作为前体分子的环状RNAs生物发生的重要信息。这项研究还表明，通过使用次要剪接体的反向剪接，RBP介导的RNA在细胞质中的环化可能。
