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    Characterization of a Novel Nuclear Specific Dicer-isoform in Human Cells

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    Name:
    Fatema Alquraish Thesis.pdf
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    1.995Mb
    Format:
    PDF
    Description:
    Fatema Alquraish Thesis
    Embargo End Date:
    2021-09-01
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    Type
    Thesis
    Authors
    Alquraish, Fatema H. cc
    Advisors
    Orlando, Valerio cc
    Committee members
    Frøkjær-Jensen, Christian cc
    Al-Babili, Salim cc
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Date
    2019-09
    Embargo End Date
    2021-09-01
    Permanent link to this record
    http://hdl.handle.net/10754/656669
    
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    Show full item record
    Access Restrictions
    At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis will become available to the public after the expiration of the embargo on 2021-09-01.
    Abstract
    For more than a decade, studies focused on RNA interference (RNAi) pathway as a pivotal gene regulatory mechanism. RNAi components are attracting considerable interest due to the recent evidence demonstrating that they play a role not only in post-transcriptional regulation but also in transcriptional level. The involvement of RNAi components in heterochromatin formation and RNA Pol II processivity and alternative splicing in different organisms has been shown. Dicer protein, a highly conserved protein among kingdoms, is one of the main effectors in this pathway. There is a considerable amount of literature on Dicer’s role in the cytoplasm; however, there is still vast ambiguity concerning nuclear Dicer. More recent evidence reveals the existence of Dicer1 variants that are differentially expressed in some cancer cells. Our experiments set out to investigate one of these variants that we hypothesise is responsible for the nuclear function. We undertook genomic and biochemical approaches applied to HAP 1 cells as a model system to characterise Dicer1-s, taking advantage of a custom-made antibody in our research group. Here, as anticipated, our experiments proved that Dicer1-s is enriched in the nuclear compartment compared to full-length Dicer1, indicating that it might be a putative contributor to nuclear gene regulation activity. Unfortunately, it was not possible to establish a mutant cell line to investigate the significant nuclear function of Dicer1-s, due to the need for further optimisation of the methods used. Exploitation of previously optimised gene knock-out tools might accelerate shedding light on protein, DNA, and RNA partners, disclosing the exact nuclear mechanisms that might exhibit similar activity.
    Citation
    Alquraish, F. H. (2019). Characterization of a Novel Nuclear Specific Dicer-isoform in Human Cells. KAUST Research Repository. https://doi.org/10.25781/KAUST-Y70HC
    DOI
    10.25781/KAUST-Y70HC
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-Y70HC
    Scopus Count
    Collections
    Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Theses

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