Regulation of immune responses by RasGEF1B circular RNA / Ng Wei Lun
Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown f...
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| Format: | Thesis |
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2017
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| Online Access: | http://studentsrepo.um.edu.my/8438/ http://studentsrepo.um.edu.my/8438/2/All.pdf http://studentsrepo.um.edu.my/8438/6/wei_lun.pdf |
| Summary: | Circular RNAs (circRNAs) constitute a large class of RNA species formed by
the back-splicing of co-linear exons, often within protein-coding transcripts. Despite
much progress in the field, it remains elusive whether the majority of circRNAs are
merely aberrant splicing by-products with unknown functions, or their production is
spatially and temporally regulated to carry out specific biological functions. To date, the
majority of circRNAs have been cataloged in resting cells. Here, this research identifies
a LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in
cytoplasm, shows cell-type specific expression, and has a human homolog with similar
properties, hcircRasGEF1B. The functional experiments show that knockdown of the
expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally,
this study demonstrates that mcircRasGEF1B regulates the stability of mature ICAM-1
mRNAs. To gain broader insights of mcircRasGEF1B function during cellular response
to LPS stimulation, targeted mcircRasGEF1B depletion with high-throughput
transcriptomic analysis is combined. The results show that knockdown of
mcircRasGEF1B results in altered expression of a wide array of genes. Pathway
analysis reveals an overall enrichment of genes involved in cell cycle progression,
mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling
pathways and macrophage activation. These findings expand the inventory of
functionally characterized circRNAs with a novel RNA species that may play a critical
role in fine-tuning immune responses during macrophage activation and protecting cells
against microbial infection. |
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